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    • 专利摘要:

    公开号:SU991944A3
    申请号:SU802875550
    申请日:1980-01-28
    公开日:1983-01-23
    发明作者:Армон Харберт Чарльз；Росс Джонсон Майкл；Шерман Мелвин Лоуренс (Младший)
    申请人:Пфайзер,Инк (Фирма)；
    IPC主号:
    专利说明:

    n, m 0.1;
    W
    - hydrogen or
    represents
    where w
    hydrogen, fluorine, CHLOR,
    0-3, provided that if n cd is hydrogen, then p o and the dotted lines indicate the presence of a double bond in one of the indicated places, substituted cycloalkanones of the formula
    (SNg
    g-ldg
    where f (, RA, 2, W and n have the indicated meanings,
    subjected to reduction with an alkali metal borohydride or diisobutylaluminum hydride in an organic solvent at a temperature of from -78 to 30 ° C.
    The compounds of formula I contain asymmetric centers at the 1,3- and 4-positions, and if the cycloalkyl group is 6-8 membered, then the 5-position of the cycloalkyl part may be an asymmetric carbon atom. In addition, they may contain additional asymmetric centers in substituents of the 4th and 5th positions and in the group (-Z-W) of the phenyl ring. The cis configuration of the substituent in the 1-position of the cycloalkyl part with respect to the phenol and substituted phenol part in the 3-position and the trans configuration of the 3- and 4-substituents and 4- and 5-substituents, respectively, on the cycloalkyl part is preferable biological activity.
    Thus, the structural formula I covers racemates, enantiomers, diastereoisomers. and diastereo measurement of the mixture.
    Preferred are compounds of the formula I, where hydrogen, RQ is hydrogen or alkyl, Rj is hydrogen or methyl, R is hydrogen or alkyl, and Z, W, etc. have the meanings indicated in t abl. one.
    Table 1" .
    .
    Alkylene having 8-11 carbon atoms
    Alkylene having 4-7 carbon atoms
    (alkyl) -O- (alkyl2) p (alkyl,) -O- (alkyl2) p
    Chlorine
    Carrying out the process at temperatures below -78s increases the selectivity of the process, the temperature contributes to the occurrence of side processes in the case of using sodium borohydride as a solvent.
    Isopropyl alcohol or dimethyl ether can be used to conduct the process at higher temperatures.
    If lithium borohydride is used as a reducing agent, the diiobutyl aluminum hydride should be carried out in anhydrous solvents (diethyl; or dimethyl ether, tetrahydrofuran, 1,2-dimethoxyethane).
    Example. Preparation of trans-cis-3-2-benzyloxy-4- (1,1-dimethylheptyl) -phenyl cyclohexanol.
    To a solution of 43.0 g (0.106 mol) of 3 - 2-benzyloxy-4- (1,1-dimethyl) phenyl. Cyclohexanium 1 in 500 ml of methanol and 15 ml of tetrahydrofuran at -40
    8.05 g (0.212 mol) of sodium borohydride are added in three portions. The reaction mixture is stirred for 1 h at -40 s, after which it is allowed to warm to and then slow down the reaction by adding 100 ml of saturated sodium chloride. 1500 ml of water are added to the reaction mixture, and the mixture is extracted with three portions of 450 ml of ether each. The mixed ether extracts are diluted with three portions of 100 ml of water and two portions of 200 ml of saturated sodium chloride, dried over magnesium sulfate and evaporated to an oil. The oil was purified on a chromatographic column with 400 g of silica gel by elution of ether-diclohexanone, to obtain, during elution, 5.0 g (12%) of trans-3-2-benzyloxy-4- (1,1-dimethylheptyl) -Anyl-cyclohexanol.
    PMR: & ccssv 0/85 (t, terminal methyl); 1.26 (s, heme-dimethyl); 3.51 (t, benzyl methin); 4.24 (t, carbinol 5 methin); 5.15 (s, benayl methylene); 6.85-7.26 (m, aromatic H) and 7.47 (m, phenyl H). . IR Spectrum (CHCU): 3636, 349.7, 1629 and 1537 cm-, Mass spectrum, m / e: 408 (m), 393, 390, 323 and 91. Elemental analysis for € 7344002: Calculated: C 82, thirty; H 9.87. Found,%: C 91.98; H 9.82. Also obtained is 22.2 g (51%) of cis-3-2-benzyloxy-4- (1,1-dimethylteptyl) -phenyl cyclohexanol, m.p. 75.5-76 ,. PMR, Scjjce 0.85 (m, terminal methyl)} 1.28 (s heme-dimethyl); 3.1. (t, benzyl methin), 3.79 (t, carbonol. methin), 5.12 (s, is benzyl methylene); 6.83-7.22 (t, aromatic H) and 7.42 (s, phenyl H). . IR spectrum (sleep C): 3636, 3497,. 1629 and 1587 cm. V Macc-cnekTp, m / e: 408 (.M), 393, 390, 323 and 91. Elemental analysis for: Calculated,%: C 82.30, H 9.87. Found,%: C 91.95, H 9.74. Similarly, the following compound A is obtained from the corresponding ketones: A.-3- | 2-Benzyloxy-4- (1, l-dimethylheptyl) phenylJ-3-methylcyclohexane nol in the form of oil from 3-2-benzyloxy-4- (1,1gdimethylheptyl) -phenyl-3-methylcyclohexanone (200 mg; 0.476.) . PMR, § JocCa terminal methyl side chain); 1.23 (s, hemdimethyl); 1.30 (s, C-3 methyl); 3.65 (p, carbinol methin); 6.00 (s, benzyl simple methylene); 6.6-7.3 (t, aromatic H) and 7.25 (t, phenyl H). IR Spectrum (CHCU): 3546, 3378, 1603 and 1555 CMV. Mass spectrum, m / e: 422 (.M), 337, 314 ,. 299, 271 and 229. B. Trans-, trans.ns-3-2-benzyloxy-4- (1,1-dimethylheptyl) phenyl} -4-methylcyclohexanol (0.225 g, 14%) in de oil and 1 , 19 g (74%) of the cis-, trans-isomer from trans-3- 2-benzyloxy-4- (1,1-dimethylheptyl) phenyl 4-methyl cyclohexanone (1.6 g, 3.8 mmol). For tpance, - trans-isomer spectrum, 8 (.dose: 0.80 (t, terminal side chain methyl and C-4 methyl)) 1.27 (s, hem-dimethyl), 3.12 (t, benzyl metin ); 4.20 (t, carbonyl methine), 5.13 (s, methylene benzyl ether); 6.95 (t, aromatic C); 7.15 (d, j, aromatic H). and 7.48 (hs, phenyl H). IR spectrum (CHCla) :. 3413, 1616 and 1575 cmH. For CIS, trans-isomer PMR, 0.70 (d, J 6 Hz, C-4, methyl), 0.85 (t, terminal methyl of the side chain); 1729 (s, heme-dimethyl); 2.81 (t, benzyl methyl); 3.75 (t, carbinol metin); 5.13 (s, methylene benzyl ether); 6.93 (t, aromatic H); 7.15 (d, J 8 Hz, -aromatic H) and 7.43 (bs, phenyl H). IR spectrum (CHCIg): 3571, 3390, 1618 and 1577 cmH Mass spectrum, m / e: 422, 337 314, 272, 229 and 91. B. Mix of cis- and trans-3 - 2-benzyloxy-4 - (1,1-dimethylheptyl) phenyl-cyclopentanol (1.1 g, 85%) as an oil is obtained from 3- {2-benzyloxy-4- (1,1-dimethylheptyl) -phenyl cyclopentanone (1.32 g, 3.37 mmol). Mass spectrum, m / e: 394 (m) 379,. 376, 309 and 91. G. trans-3- 2-Benzyloxy-4- (1,1-dimethylheptyl) -fanyl cycloheptanol (695 mg, 49%) and 380 mg of 27%) of the cis isomer are obtained in the form of an oil from 2-3 -benzyloxy-4- (1,1-dimethylheptyl) -phenyl cycloheptanone (1.40 g, 3.3.3 mmol)., cTArtS cis-isomer has - PMR, about 0.85 (t, terminal. methyl side chains), 1.30 (s, heme-dimethyl), 3.15 (t, benzyl methine); 3.90 (ha, carbonyl methine); 5.15 (5, methylene benzyl ether); bg87, 4 (t, aromatic H) and 7.45 (bs, phenyl H) .. IR spectrum (CHC1e) 3571, 3448, 1613 and 1572 CM-V Mass spectrum, m / e: 422 {M), 337, 314, 223 and 91. The trans-isomer has a PMR. :. CDCEj 0.86 (m, terminal methyl); 1.26 (s, heme-dimethyl); 3.41 (t, benzyl metin); 4.10 (jn, carbinol methin); 5.17 (s, benzyl methylene); 6.87, 2 (t, aromatic H); 7.18 (d, J: B Hz, aromatic H) and 7.45 (bs, phenyl I). IR spectrum (CHCta): 3534, 3390, 1613 and 1572 cm - Mass spectrum, m / e: 422 (M), 337, 331, 314, 246, 229 and 91. D. cis-3-2-Benzyloxy -4- {2,5-phenylpentyloxy) -phenyl-cyclohexanol (1.51 g, 76%) and its trans-isomer (0.379 g, 19%) as an oil from 3- 2-benzyl-4- (2- 5-feiylpentyloxy) phenyl cyclohexanone (2.0 g, 4.52 mmol). the trans-isomer has nMP ,, CDCBj 1.28 (d, J 6 Hz, methyl); 2.68 (m, benzyl methylene); 3.45 (m, benzyl metin); 4.22 (t, carbinol methin); 4.30 (t, sidein methin); 5.09 (s, benzyl, methylene ether); 6.45 (dd, J 8 and 2 Hz, aromatic H); 6.55 (bs, aromatic H); 7.10 (d, J 8 Hz, aromatic H); 7.25 (s, phenyl H) and 7.45 (bs, phenyl H).
    IR Spectrum (CHC1-): 3571, 3448, 1613 and 1590 cM-l
    Mass spectrum, m / e: 444 (), 298, 280, 190 and 91, TM5
    The cis isomer has nMP, Oj.
    1.25 (d, J b Hz, methyl); 3.0 (t, benzyl methin); 3.77 (t, carbinol methin), 4.38 (t, sidein metin), 5.10 (s, benzyl methine ether), 6.50 (dd, J 8 and 2 Hz, aromatic H) J 6 , 58 (bs, aromatic H); 7.12 (d, J 8 8 Hz, aromatic H); 7.32 (s, phenyl H) and 7.43 (s, phenyl H).
    IR spectrum (CHCla) 3571, 3390, 1613 and 1587,
    Mass spectrum, m / e: 444 (), 298, 190 and 91.
    E. cis-3-f2-Benzyl-4-4- (l, l-dimethyloctyl) -phenyl 3 and piclohexanol (1.35 g, 45%) and the trans-isomer (0.34 g 11.9%) of 3.00 L7 (7.14 mmol) of 3- 2-benzyloxy-4- (1,1-dimethyloctyl) -phenyl 3-cyclohexanone, and also 0.90 g (30%) of a mixture of cis and trans isomers.
    trans-isomer has a spectrum
    rms
    RMP / tf - 0.87 (t, terminal CDCD: -
    thyl side chain), 1.25 (s, heme-dimethyl), 3.50 (t, benzyl methine); 4.22 (t, carbinol methin); 5.15 (s, benzyl methylene ether) and 6.87, 6 (t, aromatic and phenyl H
    IR spectrum (CHCL): 3497, 1623 and 158 cm-.
    Mass spectrum, m / e: 422 (M) and 323.
    The cis-isomer has a PMR spectrum,
    l TMS,
    cDcev ™ terminal methyl
    side chain); 1.25 (s, heme-dimethyl 3.10 (t, benzyl methin); 3.75 (jn, carbinol methin), 5.12 (s, benzyl methylene ether); 9.91 (dd, J "8 and 2 Hz, aromatic H); 6.91 (d, J 2 Hz, aromatic H) J 7.1 (d, J 8 Hz, aromatic H) and 7.42 (bs, phenyl H).
    IR (snc): 3571, 3425. 1618 and 1577 CMl
    Mass spectrum, m / e: 422 (m) and 323.
    G. cis-3- (2-Benzyloxy-4-tert.-butylphenyl) -cyclohexanol (7.18 g, 59%), trans-isomer (1.33 g, 11%) and 1.5 t (12%) mixtures of cis and trans isomers from 12.0 g (0.0357 mol) of 3- (2benzyloxy-4-tert, -butylphenyl) cyclohexanone. .
    The cis isomer has a m.p. 78-79 C (from hexane) and PMR, with {. : 1.30 Cs i butyl)) ZDO (t, benzyl methin); 3.72 (t, carbinol methin); 5.12 (s, benzyl, methylene ether); 6.97 (d, J 2. Hz, aromatic H) j 6.97 (dd, J - 8 and 2 Hz, aromatic H), 7.17 (d, J 8 Hz, aromatic H) and 7.40 ( bs, phenyl H).
    IR Spectrum (CHCU): 3636, 3472, .1621 and 1582 cm-.
    Mass spectrum, m / e: 338 (M), 323, 320, 223, 215 and 91.
    Elemental analysis for C.:
    Calculated,%: C 81.61; H, 93.
    Found,%: C 81.79, H 8.77.
    trans isomer has,. :
    1.23 (s, t-butyl); 3.50 (m, benzyl methin), 4.20 (m, carbinol methin) 5.02 (s, methylene benzyl ether, and 6.8-7.4 (t, aromatic H and phenyl H).
    IR spectrum (CHCL): 3650, 3472, 1626 and 1587 cm-1
    Mass spectrum, m / e: 338 (M), 328, 320, 230 and 91.
    3. CIS-3- 2-Benzyloxy-4- (1,1-dimethylpropyl) -phenylZcyclohexanol (6.3 g, 78%) and the trans-isomer (1.0 g, 12%) as an oil from 8.0 g (0,0229 mol) of 3 - 2-benzyloxy-4- (1,1-dimethylpropyl) -phenyl Zcyclohexanone
    The cis-isomer has nMP, ciJJ:
    0.67 (t, J 7 Hz, terminal methyl); 1.26 (s, rem-dimethyl); 3.05 (nj / benzyl methin), 3.76 (t methyl carbinol); 5.15 (s, benzyl simple Fir methylene); 6.92 (d, J 2 Hz, aromatic H); 6.92 (dd, J 8 and 2 Hz, aromatic H); 7.17 (d, J 8 8 Hz, aromatic H) and 7.42 (bs, phenyl H).
    IR spectrum (snow-): 3636, 3344, 1626 and 1587 CNTl
    Mass spectrum, m / e: 352 (M), 337, 334, 323, 244, 215 and 91.
    The trans-isomer has an IR spectrum (ents): 3636, 1626 and 1587 CMt
    Mass spectrum, m / e: 352 (M), 337, 334, 323, 244, 215 and 91.
    Similarly, polupiot cis-3- 2-benzyloxy-4- (1,1-dimethylbutyl) -phenyl-cyclohexanol (4.16 g, 52%), trans-isomer (0.88 g, 11%) and 0.49 g (6 , 1% mixture of cis- and trans-isomers in the form of an oil from 8.0 g (0.022 mol) of 3- 2-benzyloxy-4- (1,1-dimethylbutyl) -phenyl-cyclohexanone. T / WS
    cis-Izger has nMP, (fcDcf-i 0.80 (m, terminal methyl) / 1.23 (s, heme-dimethyl); 3.05 (t, benzyl metin); 3.70 (t, carbinol metin) ; 5.08 (s, benyl ether methylene ether), 6.86 (d, J - 2 Hz, aromatic H); 6.86 (dd, J 8 and 2 Hz, aromatic H); 7.11 (dj J 8 Hz, aromatic H) and 7.35 (bs, phenyl H).
    IR (snow): 3623, 3448, 1621 and 1582 cm-1
    Mass spectrum, m / e: 366 (), 351, 348, 323, 258, 215 and 91.,
    Trans-Izmer has PMR, Oh sisvl
    0.83 (t, terminal methyl)} 1.22 (s, hem-dimetsh1); 3.40 (t, benzyl metin); 4.18 (m, carbinol methin); 5.09 (s, benzyl methylene ether), 6.86 (d, J Hz, aromatic H) 6.86 Cd, J at 8 and 2 Hz, aromatic E), 7.11 (d J 8 Hz, aromatic H ) and 7.39 (t, phenyl n). five
    IR spectrum tCHCU): 3623, 3472, 1623 and 1585 cm.
    Mass spectrum, m / e: 366 (M), 351, 348, 323, 258, 215 and 91.
    I. trans-3-C2-Benzyloxy-4- (1,1-U-dimethylheptyl) -phenyl g4- (2-propenyl) -c clohexanol (1.9 g, 13%) and cis-3, -trans- 4-isomer (7.3 g, 51%) as an oil from trans-3- 2-benzyloxy-4- (1,1-dimethylheptyl). - phenyl 1-4- (2-., -Propenyl) -cyclohexanone ( 14.3 g, f 32.1 mmol). During the elution and on silica gel with a mixture of pentane and ether (2: 1), trans-3, -cis-4-isomer of the title compound is obtained in the form of an oil, and then cis-3, -trans-4-isomer.
    The trans-3, -cis-4-isomer has an IR spectrum (СНС1з): 3559, 3401, 1639/1608 and 1567 cm-.
    Mass spectrum, (Ussevseg: 0.32 (t, 25 terminal methyl); 1.25 (s, gem-dimethyl (; 3.30 (t, benayl methine))} 4.12 (jn, carbinol metin), 4 6-5.0 (t, vinyl H) 5.06 (s, benzyl methylene) 5.2-6.1 (w, vinyl n) ;; 6.82 (d, J 30 2 Hz, aromatic H) ; 6.82 (dd, J 8/2 Hz, aromatic H); 7.07 (d, J 8 Hz, aromatic H) and 7.38 (bs, phenyl) ..
    The cis-3, trans-4-isomer has an IR-35 spectrum (CHCL): 3571, 3401, 1639, 1610 and 1572 CM-V
    Mass spectrum, m / e: 448 (M), 406, 363 and 91.
    , Gsvsee,: 0,82 (t, terminal 40
    PMR methyl), 1.22 (s, heme-dimethyl); 2.90 (t, benzyl-methin)} 3.73 (t, carbinol methin) V4, 6-5.1 (w / vinyl H);
    5.02 (s, benzyl methylene); 5.36 .3 (t, vinyl H); 6.75 (d, J 2 Hz, aromatic H), 6.75 (dd,
    J 8 and 2 Hz, aromatic n); 6.99 (d, J 8 Hz, aromatic H) and 7.25 (bs, phenyl).
    K. cis-3-C2-Benzyloxy-4- (1D-50-dimethylheptyl) -phenylZ-trans-4- (2-butenyl) -cyclohexanol (495 mg, 82%) and trans-3, -cis-4- isomer (105 mg, 18%) from trans-3-G2-benzyloxy-4- (1,1-Dimethylheptyl-1-phenyl 3- (2-butenyl) g-cyc-55 lexanone (600 mg, 1.30 mmol). First E7; yuiruyut trans-3, -Cis-4-yz6mer.
    trans-3, -is-4-isomer has a mass spectrum, m / e: 462 (M), 447, 444, 377 and 91.40
    The cis-3, trans-4-isomer has an infrared spectrum (sleep 1,): 3610, 3448, 1618 and 1577 cm-L
    Mass spectrum, m / ei 462 (M), 447, 444, 377 and 91.65
    L. cis-3-C2-Ben. Sil-6-x-4- {1,1-dimethylheptyl) -phenyl-j-trans-4- (2-pentenyl) -cyclohexanol n trans-3, -cis-4-isomer from trans-3 - (2-benzyloxy-4- (1,1-dimethylheptyl) -phenylZ-4- (2-pentenyl) -cyclohex she (497 mg,
    1.04mmol). During the elution, 84 g (17%) of trans-3, cis-4-isomer (Rj 0.26, silica gel 33% ether-pentane), 363 mg (73%) of cis-3-, trans-4- isomers (Rp 0.13, silica gel 33% ester-pentane).
    M. cis-3- 2-Vvzyloxy-4- (1,1-dimethylpentyl) -phenyl 3-cyclohexanol (5jO g, 83%) and the trans-isomer (0.60 g, 10%) as an oil from 3- 2-benzyloxy-4- (1,1-dimethyloentyl) -phenyl cyclohexanone (6.0 g, 58 mmol),
    The trans-isomer has an IR spectrum of j (СНС1з): 3636, 3497, 1623 and 1572 cm
    Mass spectrum, m / e: 380 (M).
    Spectrum nMP, (m, terminal methyl); 1,2 4 t s, heme-dimethyl) J
    3.5 (jn, benzyl methin); 4.20 (ni, carbonol metin); 5.09 (s, benzyl methylene) and 6.8-7.6 (t, aromatic H).
    The cis-isomer has an IR spectrum (CHCL 3636, 1621 and 1580 cm-.
    Mass spectrum, m / e: 380 (M),
    nMP, cQ: 0.75 (m, end
    methyl); 1.14 (s, heme-dimethyl); 2.90 (t, benzyl methin), 3.52 (go, carbinrl metin); 4.80 (s, benzyl methylene), 6.49 (dd, J - 8 and 2 Hz, aromatic I), 6.49 (d, J - 2 Hz, aromatic H)) 6.72 (d, J - 8 Hz, aromatic H) and 6.96 (L s, phenyl). N. cis-3-C2-Venzyloxy-4- (1,1-di1-datilhexyl) -phenyl cyclohexanol (3.0 g, 43%) and the trans-isomer (660 mg, 9%) as an oil from 3- 2 benzyloxy-4- (1,1-dimethylhexyl) -phenyl-Cyclohecaanone (7.0 g, 17.9 mmol).
    The cis-isomer has an IR spectrum (CHC) h): 3623, 3448, 1618 and 1575 cm M cc spectrum, M / ej 394 (M).
    PMR,
    : 0.82 (t, trailer
    nMP, 1t, terminal methyl); 1.2 (s, heme-dimethyl), 3.07 (t, benzyl methine, 3.70 (t, carbinol methin), 5.08 (s, benzyl methylene); 6.88 (dd, J 8 and 2 Hz, aromatic H); 6.88 (d, J - 2 Hz, aromatic H); 7.12 (d, J 8 Hz, “aromatic H) and 7.37 (bs, phenyl).
    .. g
    The trans-isomer has an IR spectrum. (CHC1): 3623, 7448, 1618 and 1577 cm Mass spectrum, m / e: 394 (M).
    PMR, Ustese 6.80 (ffl, terminal methyl); 1.27 (s, heme-dimethyl), 3.42 (a / benzyl methine); 4.12 (t, carbinol methin); 5.02 (s, benzyl methylene); 6.83 (t, aromatic H), 7.04 (d, J 8 Hz, aromatic H) and 7.34 {bs, aromatic H).
    Similarly, cis-3- | 2-benzyloxy-4- (1,1-dimethylnonyl) phenylJ-cyclohexane (5.0 g, 59%) and transisomer (1.0 g, 12%) are obtained in the form of an oil from 3- 2-benzloxy-4- (1,1-dimethylnonyl b phenyl} cyclohexanone (8.5 g, 19.6 mmol).
    The cis-isomer has an IR spectrum of j (SSCC): 2623, 3448, 1618 cm
    Mass spectrum, m / e: 436 (M).
    nMP, tfcKc7j 5 (j2, terminal methyl); 1.22 (s, heme-dimethyl)) 3.04 (y, beesyl label); 3.67 (t, carbinol methin) j 5.08 (s, benzyl methylene); 6.87 (dd, J "B and 2 Hz, aromatic H); 6.87 (d, J 2 Hz, aromatic H) and 7.05-7.45 (t, aromatic H and phenyl).
    The trans-isomer has an IR spectrum. (SNSC): 3610, 3448, 1618 and 1575 cm
    Mass spectrum, m / e: 436 (M). GTLL,
    PMR, Os3) Ce J (t, terminal methyl), 1.22 Gz, heme-dimethyl); 3.42 (tn, benyl methine); 4.16 (t, karbTGnol metin), 5.02 (s, benzyl methylen) and 6.7-7.5 (t, aromatic H and phenyl).
    O. cis-3-G2-Benzyloxy-4-S1,1-dimethylundecyl) -Feil cyclohexanol (3.5 g, 50%) and the trans-isomer (1.0 g, 14%) in the form of oil from 3-12 -benzyloxy-4- (1,1-dimethylundecyl) -phenyl | cyclohexanone (7.00 g, 15.0 mmol).

    The cis-isomer has an IR spectrum of j (CHCI): 3636, 3448, 1621 and 1582 cm.
    Mass spectrum, m / e: 464 (M).
    JiTNVS
    PMR, Osvsee 0.95 (tn, terminal
    methyl); 1.33 (v, heme-dimethyl), 3.09 (in, benzyl methine); 3.70 (t, carbinol methin); 5.20 (s, benzyl methylene) 6.99 (d, J 8 and 2 Hz, aromatic H); 6.99 (dd, J 8 and 2 Hz aromatic H); 7.22 (d, J 8 Hz, aromatic H) and 7.50 (bs, phenyl H).
    The trans-isomer has an IR spectrum (CHCIj) (ishroka), 1618 and 1577 cm.
    Mass spectrum, m / e: 464 ().
    . PMR, (Гjjjlg,: 0.85 (n, terminal
    methyl); 1.22 (s, heme-dimethyl); 3.48 (t, benzyl methin), 4.17 (t, benzyl metin), 5.08 (s, benzyl methylene) and 6.75-7.55 (t, aromatic, Ni phenyl).
    P. cis-3- 2-Benzyloxy-4- (1,1-dimethyldecyl) -phenyl-3 cyclohexanol (2.66 g, 59%) and the trans-isomer (0.36 g, 8%) as an oil from 3- C2-benzyloxn-4- (1,1-dimethyldecyl) -phenyl cyclohexanone (4.5 g, 10.0 mmol).
    The cis-isomer has an IR spectrum of fCHCIj) 3704, 3571, 1639 and 1597 CMt
    Mass spectrum, m / ej 450 (M).
    PMR, dcjjjjg: 0.86 (m, terminal
    methyl), 1.25 (s, heme-hymethyl) i 3.08 (W-benzyl methine); 3.74 (t, carbinol methin); 5.08 (s, benzyl methylene), 6.88 (dd, J 8 and 2 Hz, aromatic H); 6.88 (d, J 2 Hz, aromatic H); 7.12 (d, J 8 Hz, aromatic H) and 7.37 (b, s, phenyl).
    The trans-isomer has an IR spectrum (CHC1e): 3623, 3448, J.616 and 1577 cm
    Mass spectrum, m / e: 450 (M).
    PMR ,, 82 (I1, terminal methyl) J 1.22 (s, heme-dimethyl), 3.53 (m, benzyl methine); 4.22 (sh., Carbinol mebin)) 5.02 (s, benzyl methylene) and 6.8-7.6 (t, aromatic H and phenyl).
    Similarly, cis-3- 2-benzyl-6-hydroxy-4- (1,1-dimethylheptyl) -phenyl} cyclooctanol (1.36 g, and the trans-isomer (4.12 g, 59%) are obtained in the form of 3- | 2-benzyloxy oil -4- (1,1-dimethylheptyl) -phenyl-cycloactanone (7.0 g, 16.1 mmol).
    Mass spectrum: m / e: 436 (M), 421.418, 351, 328, 243 and 91.
    LTM nMP, Of.g: 0.83 (rn, terminal
    methyl); 1.28 (s, heme-dimethyl), 3.4 (bs, benzyl methine); 3.9 (t, carbinol methin) / 5.10 (s, benzyl methylene); 6.85 (t, aromatic H); 7.08 (d, J 8 Hz, aromatic H) and 7.36 (p, phenyl).
    Pr and Ie p 2. Preparation of cis- and trans-3- 2-hydroxy-4 - (- 4-phenylbutyloxyphenylZcyclohexanol.
    To a solution of 4.7 g (14.2 mmol) of 3-C2-OXI-4- (4-phenyl-butyloxy) -phenyl-3-cyclohexanone in 25 ml of methanol was added 0.539 g (14.2 mmol) of sodium borohydride.
    The reaction mixture is stirred for 40 minutes and then 250 ml of ether are added to 250 ml of saturated sodium chloride. The ether extract is passed once with 150 ml of saturated sodium chloride, dried over magnesium sulfate and evaporated to an oil. The oil is purified chromatographically on a C 400 g column of silica gel, eluting with a mixture of dichloromethane and zfir (2.5 "1), to obtain 3.37 g (70%) of the cis isomer recrystallized from cyclohexane and 0.68 g (14%) of the transisomer recrystallized from cyclohexane, and 0,69 g (14%) of a mixture of isomers.
    The cis isomer has a m.p. 79-80 C.
    , сГ J 2,70 (m, benzyl, b-jJCei-
    YOY methylene), 3.26 (t, benzyl methine), 3.93 (dt, J 6 Hz,); 4.28 (t, OH, carbinol methin, at, (f 4.25 m, metin carbinol), 6.42 (dd, j 8 and 2 Hz, aromatic H), 6.45 (d, J 2 Hz, aromatic H); 7.03 (d, J 8Tz aromatic H) and 7.22 (s, phenyl N). IR spectrum (dream b): .3610, 3333.1631 and 1603 cm. Mass spectrum, m / e: 340 () 322, 190, 91 .. Elemental analysis of length Calculated%: C-77.61; H 8-29Found,%: C 77.46, H 8.25. The trans-isomer has t square 112114 G.:.; PMR, Oci) c | j 2f68 (ji, benenlovy methylene), 3, iBO OH,, methin. carbinol, at 3.6 3, m, metin carbinol and cG 3.90, bt, J 6 Hz, —OCH) V 6j32 (bs, overlapping c (T 6.40); 6; 40 (dd, J 8 and 2 Hz, aromatic H); 7.00 (d, J 8 Hz, aromatic H) and 7.20 (phenyl H) i IR spectrum: {SNSC): 3610, 3390, 1631 and. 1595; cmH Mass spectrum, m / .e: 34.0 {M +), 322, 190 and 91. Elemental for C / ZHH-g e Calculated,%: C 77.61., H 8.29. Found,%: C 77.40, H 8.31. Similarly, a trace of the compound is obtained. A. cis-3-4- (2-Heg1Tyloxy) -2-hydroxy-phenyl diclohexanod and trans-Isomer in the form of an oil of ee ((2-heptyloxy) -2-oxyfenne-d) cyclohexanone (15.2 g. 13.6 microns). During the elution process on silica gel, 854 g (3 €%) of the cis-3 and 107 mg (3%) of the trans-3-neomero cis-isomer have a K spectrum (CHCij): 3597, 333, 1629 and 1600 cm L mass. modulus m / e: .306 (M +), 208/150, 173 and 162. nMP, (fJ: 0.82 (m, methyl); 2.8 (m, benoyloyl methine); 3.7 (t, Metink4p binol and OH (4.1 t, methin); 6.38 (t, aromatic H) and 6.93 (d, J 8 Hz, aromatic H) the trans-isomer has a mass spectrum, m / e: 306 Cm ), 208 and 190. PMR,: 0.28 (m, methyl), 3.25 (t, ben3yl 4etine); 4.3 (t, metric of Karbinol and O8), 6.33 (t, aromatic .H) and 6.94 (d, J 9 Hz, aromatic H). B. cis-3- 4- (2-Octyloxy) -2-hydroxy-phenyl} cyclohexano and trans-isomer from 3-4- 2-octyloxy) -2-hydroxyphenyl3 cyclohexanone (2.92 g, -9.18 mmol B by elution on silica gel, 1.58 g (54%) of cis-3 and 0.57 g (19%) of trans-3-isomers are obtained. The cis-Iomer has an IR spectrum (SNRC) of 3663, 3390, 163 # and 1608 cm Mass - spectrum, m / et 320 (M), 319, 208 and 190. nMP, tfcDceV ® - etsh1) 2.81 (w / benzoyl 4 net), 3.8 (w / methine carbiole); 4.1 (in, metinbokoy chain and HE); 6.35 (t, arrmatic H) and 6.96 (d, J 8 Hz, aromatic u). The trans-isomer has an IR spectrum (CHCl3): 3636, 3390, 1634, and 1595 cm. Mass spectrum, m / e: 320 (H), 225, 208 ,. 190 and 173 .. "atil); 3.25 (t, benzyl methin) -, 4.1-4.9 (t, carbinol metins and side chains and OH), 6., 35 (t, aromatic H) and 6.96 (d, J - 8 Hz , aromatic H). B. cis-3-C4- (2-nonyloxy) -2-hydroxyphenyl} cyclohexanol and the trans isomer from 3-101- {2-nonyloxy) -2-hydroxyphenyl1 cyclohexanone (3.15 g, 19.48 mmol). In the process of eligibility of silica gel, 2.11 tons (67%) of cis-3 and 0.32 g (10% of V-trans-3 isomers in the form of oil are obtained. The cis-isomer has an IR spectrum. (CH2Cl): 3663, 3390, 1639 and 1610 cm. Mass spectrum, m / e: 334 (M), 816, 208 and 190.% MP, o, 88 (m, methyl), 2.85 (t, benzyl methine) 3.5- 4, D (w, metin carbinol and OH), 4.32 (p, sidein metin), 6.38 (t, aromatic H) and 6.97 (d, J 8 Hz,, aromatic n) .trans - The isomer has an IR spectrum. (Dream C): 3636, 3413, 1637 and 1592 cm. Mass spectrum, m / e: 334 (M), 316,. 208, 206 and D90. PMR,: 0.88 (t, methyl); 3.23 (t, benzyl methyl)) 3.9-4.6 (ffl., metins of carbinol and side chain and it) i 6.36 (m, aromatic and) and 6.96 ( d JS Hz, and Romatic H). G. cis-3-t4- (2- (4-phenyl) -butyloxy) -2-hydroxyphenylZcyclohec: eanol and. the trans isomer from 3-E4- (2- (3-phenyl) -butyloxy) -2-hydroxyphenyl 3-cyclohexanone (2.9 g, 8.23 mmol). During the elution on silica gel, 1.29 g (44%) of cis-3 and 241 mg (8%) of trans-3-ismers are obtained. The cis-isomer has a melting point of 96-105 0 (from pentane). IR spectrum (CHCL): 3636, 3390, 1634 t, 1608 syu-g Mass spectrum / m / es 340 (M), 322, 208, 190, 162, 147, 136 and 91. PMR, (1HZO (d, J 6 Hz, methyl) V 3.75 (t, metin carbinol); 4.23 (SHU methin side chain), 6.21 (d, J 2 Hz, aromatic Hi; 6.98 (d J 8 and 2 Hz, aromatic n); 6.98 (d, J 8 Hz, aromatic n) and 7.20 (s, phenyl). Elemental analysis for Calculated,%: C 77.61, H 8.29. Found,%: C 77.59; H 8.18. The trans-isomer has an IR spectrum, (CHCl-i): 3623, 3390, 1637 and 1595 cm Mass spectrum, m / e 340 (M), 342, 208, 190, 162 , 147, 136 and 91. nMP, (fc5cta ,.: 1.30 (m, J 6 Hz, methyl), 3.3 (t, benelyl methyl) J 4.23 (t, carbinol methyn and side chain); 6.38 (w, aromatic .H)) 6.94 (d, J 8 Hz, aromatic H) and 7.18 {S, phenyl), D, cis-3-X4 - (2- (6-Phenyl) -hexyloxy) -2-hydroxyphenyl-3cyclohexanone and the trans-isomer from C4- (2- (6-phenyl) - hexyloxy) -2-hydroxyphenyl cyclohexanol (3.3 g, 9.01 mmol). In the process of elution on silica gel, 1.54 g (46%) of cis-3 and 274 mg (8%) of trans-3- isomers, the cis-isomer has m. pl. 99-113С (from pentane). PC Spectrum (CHCL): 3636, 3367,. 1631 and 1592. Mass spectrum, m / e: 368 (M), 350, 208, 190, 162, 147, 136 and 91. HLT PMR, Os1.SVz 1gZO (d, J 6 Hz, methyl); 3.6 (t, metin carbinol), 4.2 ((p, sidein metin), 6.37 (t, aromatic H) 6.98 (d, J 8 Hz, aromatic H) and 7.18 (s, phenyl H). Assay analysis for C.JA) g. Calculated,%: C 78.22; H 8.75. Found,%: C 78.05; H 8.56. The trans-isomer has an IR spectrum (SSCS): 3636, 3413, 1634 and 1597 cm. Mass spectrum, m / e: 368 (M), 350, 208, 190., 162, 147, 136 and 91. PMTC; OSOS ,,: 1,25 (d, J 6 Hz, methyl); 4.21 (t, metins of carbinol and side chain); 6.37 (t, aromatic H); 6.95 (d, J 8 Hz, aromatic H) and 7.15 (s, phenyl H). Example 3. Obtaining (1,1-dimethylheptyl) -2-hydroxyphenyl-2-cyclohexenol. To a solution of 1.00 g (3.18 mmol) of 3-G4- (1,1-dimethylheptyl) -2-oxypheyl-α-cyclohexenone in 60 ml of ether, is added dropwise 6.3 ml of 1 M (in toluene) solution diisobutylaluminum hydride. The reaction mixture is stirred for another 30 minutes at and then added to 1.5 liters of vada. The reaction mixture was extracted with three portions of 400 ml of ether, and the mixed extracts were washed twice with 125 ml of saturated sodium chloride and dried over magnesium sulfate. After evaporation, the crude product is purified on a chromatographic column, eluting with ether, to thereby yield an oil. Crystallizing the oil from pentane gives 256 mg (25%) of the desired product, so pl. 8788C. Mass spectrum, m / e: 316 (), 298, 231 and 213. PMR, DG (t, terminal VXJCK is methyl); 4.37 (t, metin carbinol); 5.90 (t, vinyl H); 6.37 (b, OH) and 6.87 (t, aromatic H). Elemental analysis for); Calculated,%: C 79.70; H 10.19. Found,%: C 79.68; H 9.96. PRI and MER 4. Obtaining (1,1-dimethylheptyl) -2-oxyphenylJ-cyclohex-3-ene-1-ol. 1.9 g (50 mmol) of sodium borohydride was added to a solution of 17.5 g (50 mmol) (1,1-dimethylheptyl) -2-hydroxyphene7 Chlocyclohex-3-enone in 50 ml of methanol. The reaction mixture is stirred for 30 minutes and then 250 ml of ether are added to 250 ml of saturated sodium chloride. The ether extract is washed once with 250 ml of saturated sodium chloride, dried over magnesium sulphate and evaporated. The residue is purified by chromatography on a 400 g silica gel column, eluting with a 50% ether-pentane mixture, to thereby give the desired compound. Example5. Preparation of (1,1-dimethylheptyl) -2-hydroxyphenyl-cyclohex-2-ene-1-ol. To a solution of 70.0 g (0.20 mol) of 3-C 4- (1,1-dimethylheptyl) -2-hydroxyphenylZcyclohex-2-enone in 200 ml of methanol was added 7.6 g (0.20 mol) of borohydride on three . The reaction mixture is stirred for 30 minutes and then 1 l of ether is added to 1 l of saturated sodium chloride. The ether extract is washed once with 500 ml of saturated sodium chloride, dried over magnesium sulphate and evaporated. The residue was purified by chromatography on a column of 500 g of silica gel, eluting with a 50% ether-pentane mixture, to thereby give the desired compound. PR and MERP 6. Obtaining 3 - 2-hydroxy-4- (1,1-dimethylheptyl) -phenylJ-1-methylenecyclohexane. To a 50% mixture of sodium hydride and mineral oil (28 g, 48 mmol), washed with 3x25 ml of pentane, add 90 ml of anhydrous dimethyl sulfoxide, and the mixture is heated at 70 ° C for 0.75 h. Then, 17, 79 g (51 mmol) of triphenylphosphonium bromide. The yellow solution is stirred for 30 minutes at and then 2.26 g (6.3 mmol) of 3-p2-hydroxy-4- (1,1-dimethylheptyl) phenyl-cyclohexanone dissolved in 90 MP of dimethyl sulfide are immediately added, and the mixture is heated at 63-65 ° C for another 15 hours. The reaction mixture is then poured into 150 ml of ice-water (25 g MHHCO3) and extracted with 3x50 MP of ether. The mixed ether extracts are dried on A HgSQ4. g are decolorized with charcoal and otfidrrvaeEy through a layer of silica gel, obtaining a colorless oil, which is subjected to chromatography on 75 g of silica gel (eluirukhky solvent - cyclhexane). , as a result, get the target product in the form of a colorless oil. In a similar way, the cycloaclanone and cycloalkenone compounds described are converted into their corresponding methylene derivatives. Example 7. Preparation of β-benzyl-6-hydroxy-4- (1,1-dimethylheptyl) -phenyl-3-trans-5-methyl-cyclohexanol and trans, -cis-isomer. To a solution of trans-3-E-benzyloxy-4- {1,1-dimethyl-heptyl) -phenyl-5-methylcyclohexanone (300 mg, 10.714 mmol in methanol (15 ml) and tetrahydrofuran (5 ml) at -78 ° C are added 216 mg of sodium borohydride (5.68 mmol for 1 hour). The reaction mixture is stirred for 2 hours more, heated to room temperature and evaporated with like water. The residue is acidified with dilute hydrochloric acid and extracted with ether. The extract is dried over magnesium sulfate, evaporated and the residue is purified by chromatography on a roller with 50 g of silica gel, eluting with a 30% mixture of ether-penta , thus obtaining as a result of the elution of 23 mg (77%) of the trans, cis-isomer and 45.9 mg (15%) of the cis, -trans-isrme, transP, -cis-Isomer, has a mass spectrum, m / er 422 (M), 337, 314, 22 and 91. .., HSR, (: 0.86 (p, terminal methyl), 1.05 (d, J 7 Ha., C-5 methyl) J 1.26 ( s, heme-dimethyl); 3.70 (n, benzylLove methine); 4.05 (n, carbonyl methine) 5.13 (s, benzylC4Y methylene)} 6.8-8.0 (n, aromatic II ) and 7.1-7.6 (n, arrmatic H and phenyl). The cis, α-trans-isomer has a mass spectrum, m / e 422 (H-), 337, 314, 22, 206 and 91. PMR, | Gc0rti I 0.9 (n, terminal methyl); 1.05 (d, J 7 Hz, C-5 methyl) / 3.1-4.3 (n, benzyl, carbinol methines); 5.13 (s, benzene methylene)) 5.40 (s, OH) and 6.8-7,. (P, feil and aromatic H). At a mpere 8. Preparation of cis-3-C 2-benz1xxy-4- (1 ;, 1-di-heptyl-phenyl-3H-3-methylcyclhexanol and trans, -trans-isomer. To a solution of cis-3-C2-benzyloxy-4- (1D-dcmethylheptyl) -phenyl 3-5methylcyclohexanone (228 mg, 0.543 mmol) in methanol (10 ml) while sodium borogitfid (160 mg, 4.21 µl) is added in the flow for 2 hours. The reaction mixture is allowed to warm to room temperature and then added to a saturated solution of sodium chloride, ether. The ether extract is dried over magnesium sulfate and evaporated under reduced pressure. The residue is purified on a preparative chromium An ographic layer on five silk gel plates 20 cm X 20 cm X 0.5 mm, was eluted with a 50% ether-pentane mixture, to obtain 36 mg (16%) of the trans, trans-isomer (0.25, snickel, 33% -111 ether-: petroleum ether) and 168 mg (R 0.17, silica gel, 533% ether petroleum ether) cis, -cis isomer. EXAMPLE 9 Preparation of cis-3-. (1 , 1-dimethylheptyl) -2-hydroxyphenyl-5-methylcyclhexanone, To a solution of cis-3-f (1,1-dimethylheptyl) -2-hydroxyphenyl} -5-methylhexanol, (896 mg, 2.13 mmol) and 30 ml methanol is added with sodium borohydride (805 mg, 21.8 MUH). The reaction mixture is re-e11 "heated for 1 hour during heating. ayut to room temperature, H drbavl dissolved in ether and nasyeteniomu; chl 5ristomu sodium. The ether extract desiccated over Mai sulphate and evaporated to give an oil. Crystallization from pentane gives 589 mg (65%) of the title compound, m.p. 113-1140C. IR spectrum (CHCU): 3636, 3390, 1631 and 1592 cmH Mass spectrum, m / e: 332 (M), 314, 247, 229 and 95. TUI 5 PMR, .-: {t, C-5 and end,. methyl), 1.21 (s, heme-dimethyl), 2.95, benzyl methine); 3.82 (p, methyl carbinol); 5.62 (s OH), 6.82 (p, aromatic H) and 7.12 (d. J 8 G, aromatic H). Elemental analysis for t Calculated,%: C 79.46 1G 10.91. Found% j C 79.79 and 10.62. Similarly, the following compounds are obtained. And cis-3-G4- (1,1-Dimethylheptyl) -2-hydroxyphenylT-cis-5-ethylcyclohexanol (0.74 g, 74%) of c s-3-C4- (1,1-dimethylheptyl) - 2-hydroxyfenyl 3-5-ethylcyclohexanoia (1.00 g, 2.30 "base). T. pl. 110-111 ° C. IR spectrum (ency) g 3636.3367.163 and 1537 PNR: 0.90 (p / terminal methyl); 1.22 (s, heme-dshketily) {2.95 (p, benzyl methine), 3.85 (p, metin carbinol) i 5.59 (s, OH) / 6.85 (nV arszhatichesky H) and. 7.10 (d, J 8 Hz, aromatic H).,. Elemental analysis for C.) Calculated,%: C 79.71j H 11, OB. Found,%: C 79.41; H 10.71. B. cis-3-C4- (1,1-Dimethylheptyl) -2-hydroxyphenyl 3-cis-5-n-propyl cyclohydroxyne (0.954 g, 71%) from cis-3-4- (1,1-dimethylheptyl) - 2-hydroxyphenylZ-5 n-propylcyclohexanone (1.34 g, 3.74 mmol). T, pl. 103-104 ° C (from pentane). IR spectrum (SNSC): 3636, 3378, 1626 and 1587 cm Mass spectrum, m / e: 360 (M), 342, 275, 257 and 161 .. llt, c-DU 1. (n, terminal methyls ); 1.22 (s, heme-dimethyl), 2.9 (p, benzyl methin) j 3.82 (p, metin carbinol) j 5.42 (s, OH); 6.85 (p, aromatic H) and 7.08 (d, J 8 Hz, aromatic H). Elemental analysis for 0 ,. Calculated,%: C 79.94; H 11.18. Found,%: C 79.88; H 11.22. E. cis-3- 4- (1,1-Dimethylheptyl) -2-hydroxyphenyl-2-cis-5-n-hexylcyclogeanol is obtained from cis-3-.4- (1,1-Dime tylheptyl) -2-hydroxyphenyl} -5-n-hexylcyclohexanone (1.20 g, 3.00 mmol) after purification with 120 g of silica gel, eluted with a 50% mixture of sufir pentane, with a quantitative yield in the form of an oil containing traces of the trans-trans isomer, And -spectrum (CHCU): 3623, 3355, 1626 and 1585 cm Mass spectrum, m / e: 402 (M), 384, 317 and 299. nMP, (fj-.: 0.90 (n, terminal methyls); 1, 22 (s, heme-dimethyl); 2.9 (p, benzyl methin); 3.85 (p, metin carbinol); 4.32 (p, metin carbinol trans-, trans-isomer); 5.58 (bs , OH); 6.85 (p, aromatic H) and 7.09 ( d, J 8 Hz, aromatic EXAMPLE 10 dis-3-2-benzyl (1,1-dimethylheptyl) -phenyl cyclohexanol and the trans-isomer To a solution of 43.0 g (0.106 mol) 3- 2-benzyloxy-4- (1,1-dimethylheptyl) -phenyl cyclohexanone in 500 ml of methanol and 15 ml of tetrahydrofuran at -40 ° C is added in three portions of 8.05 g (0.212 mol) of sodium borohydride. The reaction mixture is stirred ) t for 1 h at -40 ° C, then allowed to warm to -10 ° C, and then the reaction is replaced by adding 100 ml of saturated sodium chloride. The reaction mixture is added to 1500 ml of water, and the mixture is extracted with three portions mi 450 ml simple. The mixed ether extracts are washed with three portions of 100 ml each of water and two portions of 200 ml each of saturated sodium chloride, and dried. sulphate magnesium sulfate and evaporate to an oil. The oil was purified on a chromatographic column on 400 g of silica gel, eluting with a 20% ether-cyclohexane mixture, to give 5.0 g (12%) of trans-3-C2-benzyloxy-4-1, 1-dimethylheptyl) - phenyl cyclohexanol. Spectrum nMP, dc-p, g ,,: 0.85 (m, terminal methyl); 1.26 (s, heme-dimethyl), 3.51 (t, benzyl methyl), 4.24 (t, carbinol methin), 5.15 (s, benzyl methylene); 6.85-7.26 (t, aromatic H) and 7.47 (t, phenyl H). IR spectrum (sleep C): 3636, 3497, 1629 and 1587 cm-1 Mass spectrum, m / e: 408 (), 393, 390, 323 and 91. Elemental analysis for: Calculated,%: C 82.30 H 9.87. Found,%: C 81.98; H 9.82. 22.2 g (51%) of the cis isomer are also obtained, with an mp. 75,576. PMR, SG .. p; 0.85 (t, terminal methyl); 1.28 (s, heme-dimethyl)) 3.1 (t, benzyl methyl); 3.79 (t, carbonol metin); 5.12 (s, benzyl methylene); 6.83-7.22 (t, aromatic H) and 7.42 (s, phenyl H). IR spectrum (sleep C): 3636, 3497, 1629 and 1587 Mass spectrum, m / e: 408 (M), 393, 390, 323 and 91. Elemental analysis for C ffl J zCalculated,%: C 82.30 ; H 9.87. Found,%: C 81.95; H 9.74. Similarly, the following compounds are obtained from the corresponding ketones A. 3- 2-Benzyloxy-4- (1,1-dimethylheptyl) -phenyl 3-3-methylcyclohexanol as an oil from 3-; 2-benzyloxy-4- (1,1- dimethylheptyl) -phenylZ-3-methylcyclohexanone (200 mg, 0.476 mmol). PMR / terminal methyl side chain); 1.23 (s, hemdimethyl); 1.30 (s, C-3 methyl); 3.65 (t, carbinol methin), 5.00 (s, benzyl simple methylene); 6.6-7.3 (t, aromatic H) and 7.25 (t phenyl H). IR spectrum (sisi): 3546, 3378, 1603 and 1555 cm-. Mass spectrum, m / e: 422 (M-b), 337, 314, 299, 271 and 229. B. trans, -trans-3-2-Benzyloxy-4- (1,1-dimethylheptyl) -phenyl 3- 4-methylcyclohexanol (0.225 g, 14%) as an oil and 1.19 g (74%) cis, the trans isomer from trans-3-G2-benzyloxy-4- (1,1-dimethylheptyl) -phenylJ-4- methylcyclohecanone (1.6 g, 3.8 mmol) .. The isomer has a PMR, cG (,,. p: 0.80 (in, terminal methyl of the side chain and C-4 methyl), 1.27 (s, heme- dimethyl);
    3.12 (m, benzyl methin), 4.20
    (m, carbinol methin), 5.13 (s,
    methylene benzyl ether),
    6.95 (t, aromatic H) i 7.15
    (d, J 8 Hz, aromatic H) and 7.48
    (bs, phenyl H).
    IR spectrum (CHCU): 3413, 1616 and 1575 cm-1
    Mass spectrum, m / e: 422 (), 407, 337 314, 272, 229 and 91..
    cis, trans-isomer has PMR, cG
    0.70 (0.70 d, J 6 Hz, C-4 methyl);
    0.85 (t, terminal methyl of the side chain), 1.29 (s, heme-dimethyl), 2.81 (t, benzyl methyl), 3.75 (t, carbinol methin); 5.13 (s, methylene benzyl ether), 6.93 (t, aromatic H)) 7.15 (s, J 8 Hz, aromatic H) and 7.43 (bs phenyl H).
    IR (CHCl1): 3571, 3390, 1618 and 1577 cm-1
    Mass spectrum, m / e: 422, 337, 314, 272, 229 and 91.
    B. A mixture of cis- and trans-3-G -benzyloxy-4- (1,1-dimethylheptyl) -phenyl cyclopentanol (1.1 g, 85%) as an oil from 3-G2-benzyloxy-4- (1, 1-dimethylheptyl G-phenyl 3 cyclopentanone (1.32 g, 3.37 mmolL
    Mass spectrum, m / e: 394 (m), 379, 376, 309 and 91.
    G. trans-3- 2-benzyloxy-4- (1,1-dimethylheptyl) -phenyl 3-cycloheptanol (695 mg, 49%) and 380 mg (27%) of the cis isomer in the form of an oil from 3- 2-benzyloxy-4- (1 , 1-dimethylheptyl) -phenylZcycloheptanone (1.40 g, 3.33 mmol) The cis-isomer has a PMR,:
    swsee
    0.85 (t, terminal side chain methyl); 1730 (s, heme-dimethyl), 3.15 (t, benzyl methine)). 3.90 (t, carbinol methin), 5.15 (s, methylene benzyl simple eLira), 6.8-7.4 (t, aromatic H) and 7.45 (bs, phenyl H).
    IR spectrum (SNSC): 3571, 3448, 1613 and 1572 cm -
    Mass spectrum, m / e; 422 (M +), 337, 314, 229 and 91.
    Trans-Isomer has PMR,.,:
    0.86 (t, terminal methyl) / 1.26 (s, hem-dimethyl); 3.41 (t, benzyl metin); 4.10 (t, carbinol methin), 5.17. (S, benzyl methylene); 6.87, 2 (t, aromatic H) J tDv (d, J 8 Hz, aromatic H) and 7.45 (bs, phenyl H).
    IR spectrum (SNS),): 3534, 3390, 1613 and 1572 CM-l
    Mass spectrum, m / e: 422 (M), 337, .331, 314, 246, 229 and 91.
    D. cis-3-G2-Benzyloxy-4- (2,5-phenylpentyloxy) -phenylZcyclohexanol (1.51 g, 76%) and trans-isomer (0.379 19%) & as an oil from 3-C2-benzyloxy-4- 2- (5-phenylpentyloxy) - eilHJiJcyclohexanone (2.0 g, 4.52 lmol). The trans-isomer has a PMR, ("
    all
    1.28 (d, J - 6 Hz, methyl), 68 (jfl, benzyl methylene); 3.45 (jn, basil methin) 4.22 (jn, carbinol mettin), 4.30 (t, side chain methin);
    5.09 (s, benzyl methylene ether), 6.45 (dd, J 8 and 2 Hz, aromatic H) 6.55 (bs, aromatic H); 7.10 (d, J -8 Hz, aromatic H) and 7.25 (s, phenyl H).
    IR spectrum (CHCU): 3571, 3448, 1613 and 1590 cm-1
    Mass spectrum, m / e: 444 (M-), 298, 280, 190 and 91.
    The cis isomer has a PMR, cG:
    1.25 (d, J -6 Hz, methyl); 3.0 (t, benzyl methin); 3.77 (t, carbinol methin); 4.38 (gp, methin of the high chain)
    5.10 (s, benzyl methine ether) 6.50 (dd, J 8 and 2 Hz, aromatic H); 6.58 (bs, aromatic H) 7.12 (d, J 8 Hz, aromatic H) J 7.32 (s, phenyl H) and 7.43 (s, phenyl H).
    IR spectrum (SNSC): 3571, 3390, 1613 and 1587 cm.
    Mass spectrum, m / e: 444 (H), 298, 190 and 91.
    E. cis-3- 2-Benzyloxy-4- (1,1-dimethyloctyl) -phenyl} cyclohexanol (1.35 g, 45%) and the trans-isomer (0.34 g 119%) of 3.00 g ( 7.14 mmol) 3-12-benzyloxy-4- (1,1-dimethyloctyl) -phenyl 3-cyclohexanone, as well as 0.90 g
    (30%) CIS-, trans-mixture.
    I
    trans isomer has. Poland, t
    0.87 (m, terminal methyl of the side chain), 1.25 (s, heme-dimethyl); 3.50 (t, benzyl methin) 4.22 (t, carbinol methin); 5.15 (s, benzyl methylene ether) and 6.8-7.6 (t, aromatic and phenyl H).
    IR spectrum (CHCL): 3497, 1623 and 1582 cm-.
    Mass spectrum, m / e: 422 (I) and 323.
    The cis-isomer has a PNR, tfJiJi "
    V T7C v
    0.85 (rn, terminal side chain methyl); l725 (s, heme-dimethyl) J 3.10 (m, benzene metin), 3.75 (m, carbinol metin); 5.12 (s, benzyl, methylene ether); 6.91 (dd, J 8 and 2 Hz, aromatic H); 6.91 (d, J 2 Hz, .aromatic H); 7.17 (d, 4J 8 Hz, aromatic H) and 7.42 (bs, phenyl H).
    IR spectrum (CHCU): 3571, 3425, 1618 and 1577 cm
    Mass spectrum, m / e g 422 () and 323.
    G. cis-3- (2-Benzyloxy-4-tert.-butylphenyl) cyclohexanol (7.18 g, 59%), trans-isomer M (1.33 g, 11%) and 1.5 g (12%) mixtures of cis and trans eomers from 12.0 g {0.0357 mol) of 3- (2-bvnzyloxy-4-ter, -butylphenyl) -cyclohexanone. Cis-Izokyur has t, pl. 78-79 ° C (from hexane). PMR, 2m | : 1.30 (s, 1- (5util), .3.10 (gp, benzyl metin); 3.72 (t carbiol metin), 5.12 (j, benzyl, methylene ether) 6.97 (d , J 2 Hz, aromatic H) 6.97 (d, .J -8 and 2 Hz, aromatic H), 7.1 (d, J 8 Hz, aromatic H) and 7.40 (bs, phenyl H). IR spectrum (SNSI): 3636, 3472, 1621 and 1582 Mass spectrum, m / e: 338 (M), 323, 320, 230, 215 and 91 ... Elemental analysis for Calculated,%: C 81.61 / H 8.83, Found,%: C 81.79, H 8.77. The trans-isomer has a PMR (.. s iUv / E 1.23 (s, t-butyl); 3.50 (jn, benzyl methin), 4.0 (t, carbinol methin 5.02 (s, benzyl, methylene ether and 6.8-7.4 (t, aromatic H and phenyl H). IR spectrum (CHCIj): 3650, 3472 , 1626 and 1587 cm. Mass spectrum, m / e : 338 (M), 323, 320, 230 and 91. 3. cis-3-2-benzyloxy-4- (1,1-dimethylpropyl) -phenyl cyclohexanol (6.3 g, 78%) and the trans-isomer ( 1.0 g, 12%) in the form of oils from 8.0 g (0.0229 mol) of 3- -benzyloxy-4- (1.1 dimethylpropyl) -phenyl cyclohexanone. The cis-isomer has nMP, tfIi J 0, 67 (t, J - 7 Hz, terminal methyl) j 1.26 (s, heme-dimethyl) j 3.05 (m, benzyl methine), 3.75 (t, methyl carbinol), 5.15 (s, benzyl methylene ether), 6.92 (dd, J - 2 Hz, aromatic H) 6.92 (d, J - 8.2 Hz, aromatic H), 7.17 (d, J 8 Hz, aromatic H) and 7.42 (bs, phenyl H). IR spectrum (CHCU): 3636, 3344,: 1626 And 1587 cm-1 Mass spectrum, m / e: 352 (M), 337, 334, 323, 244, 215 and 91. The trans-isomer has an IR spectrum . {SNSC) “3636, 1626 and 1587 CM-t Mass spectrum, m / e: 352 (M), 337, 334, 323, 244, 215 and 91. I. cis-3-C2-Benzyloxy-4- ( 1.1 dimethylbutyl) phenylZcyclohexanol (4.16 g, 52%), trans-isocure (0.88 g, 11%) and 0.49 g (6.1%) of a mixture of cis- and trans-isomers in the form of oils from 8.0 g (0.022 mol) of 3-C2-benzyloxy-4- (1,1-dimethyl-butyl) -phenyl-cyclohexanone. The cis-isomer has a PMR, cgst5 | h "0.80 (t, terminal methyl); 1.23 (s, heme-dimethyl); 3.05 (t, benzyl metin); 3.70 (t, carbinol methin), 5.08 (s, benzyl, methylene ether: i6.86. (Dd, J - 2 Hz, aromatic H) 6.86 (dd, J = 8 and 2 Hz, aromatic H); 7.11 (d; J "8 Hz, aromatic H) and 7.35 (bs, phenyl H). IR spectrum (sleep): 3623, 3448, 1621 and 1582 cm-1 1 l A- Wu Mass spectrum, m / e: 336 (M), 351, 348, 323, 258, 215 and 91. The trans-isomer has a PMR, O (.. p. T 0.83 (m, terminal methyl), 1 , 22 (s, heme-dimethyl); 3.40 (t, basic methylene) j 4.18 (m, carbinol metin); 5, Q9 d, benzyl methylene ether, 6.86 (d, J 2 Hz , aromatic H), 6.86 (dd, J 8 and 2. Hz, aromatic H) 7.11 (d, J 8 Hz, aromatic H) and 7.39 (w, phenyl H). IR spectrum (see I ,,): 3623, 3472, 1623 and 1585 cm-1 Mass Spectrum, m / e: 366 (M), 351, 348, 323, 258, 215, and 91. C. trans-3-f2-Benziloxy-4- (1, l-dimethyl-heptyl) -phenyl3-cis-4- (2- propenyl) -cyclohexanal (1.9 g, 13%) and cis-3, trans-4-isomer (7.3 g, 15%) as an oil from traNs-3-C2-benzyloxy-4- (1, 1-dimethylheptyl) -phenyl3-4- (2-propenyl) cyclohexanone (14.3 g, 32.1 mmol). In the course of elution on silica gel with a mixture of pentane and ether (2: 1), trans-3, the cis-4-isomer in the form of an oil, and then ghis-3, the trans-4-isomer are obtained. The trans-3, - cis-4-isomer has an infrared spectrum (in the sleep and): 3559, 3401, 1639, 1608 and 1567 CM. PMR, cfJJJ I 0.82 (m, terminal.%. - methyl); 1.25 (s, heme-dimethyl) 3.30 (jn, benzyl methine); 4.12 (t, carbinol methin) i 4.6-5.0 (m, vinyl H); 5.06 (s, benzyl thylen); 5,, 1 (t, vinyl H); 6.82 (d, J 2 Hz, aromatic H) 6.82 (dd, J 8 and 2 Hz, aromatic H); 7.07 (d, J 8 Hz, aromatic H) and 7.38 (bs, phenyl). The cis-3, -trans-4-isomer has an infrared spectrum (see C): 3571, 3401, 1639 and 1610 and 1572 CMt Mass spectrum, m / e: 448 (M), 406, 363 and 91. PMR, Os1) Ces 0.82 (jn, terminal methyl), 1.22 (s, heme-dimethyl) J 2.90 (t, benzyl methine); 3.73 (t, carb nol metin)} 4.6–5.1 (t, vinyl H); 5.02 (s, benzyl methylene), 5.3-6.3 (t, vinyl H) 6.75 (d, J - 2 Hz, aromatic H), 6.75 (d, J 8 and 2 Hz, aromatic H); 6.99 (d, J 8 Hz, aromatic H) and 7.25 (bSn phenyl). , L. cis-3-H2-Benzyloxy-4- (1,1-dimethylheptyl) -phenyl 3-trans-4- (2-butenyl) cyclohexanol (495 mg, 82%) and trans-3-cis-4-isomer (105 mg, 18%) from trans-3-G2-benzyloxy-4- (1,1-dimethylheptylT-feiyl3- (2-butenyl) cyclohexanone (600 mg, 1.30 mmol). Trans-3, -dis- The 4-isomer was first eluted. The trans-3, -cis-4-isomer has a mass spectrum; m / e: 462 (M), 447, 444, 377 and 91. The cis-3, -trans-4-isomer has an IR spectrum (СНС1 ): 3610, 3448, 1618 and 1577 cm. Mass spectrum, m / e: 462 (M-), 447, 444, 377 and 91. M, cis-3-2-Venzyloxy-4- (1,1- di methylheptyl) -phenyl-trans-4- {2-pvnt nyl) cyclohexanol and trans-3, -cis-4-isomer from trans-3-C2-benzyl-xy-4- (1,1-dimethylheptyl) -f Enyl-4- (2-pv tenyl) cyclohexanone (497 mg, 1.04 mmol). During the elution, 84 mg (17%) of trans-3, cis-4-isomer (R 0.26, silica gel, 33% ester-pentane) and 363 mg (73%) of 1..is-3, - trans-4-isomer (R 0.13, silica gel, 33% ether-pentane). N. cis-3-C2-Benzyloxy-4- (1,1-di methylpentyl) -phenyl cyclohexanol (5.0 g, 83%) and the trans-isomer (0.60 g of 10%) in the form of oils from 3- C2-benzylox-4- (1,1-dimethylpentyl) -phenylsidlohexanone (6.0 g, 58 mmol), the trans-isomer has an IR spectrum (CHC): 3636, 3497, 1623, and 1582 cm Mass spectrum, m / e: 380 (M). PMR, : 0.83 (t, terminal ClJCbJ-methyl); 1.24 (s, heme-dimethyl); 3.5 (t, benzyl methin), 4.20 (t, carbinol methin); 5.09 (s, benzyl methylene) and 6.8-7.6 (t, aromatic H). cis isomer IR spectrum. (Ij dream): 3636, 1621 and 1580 cm. Mass spectrum., M / «: 380 (M). nMP,: 0.75 (m, terminal methyl); 1.14 (s, heme-dimethyl) J 2.90 (t, benzyl methine); 3.52 (t, Carbinol Metin); 4.80 (s, benzyl methylene), 6.49 (dd, J 8.2 Hz, aromatic H); 6.49 (dd, J 2 Hz / aromatic H) :) 6.72 (d, J - 8 Hz aromatic H) and 6.96 (bs, phenyl) O. cis-3-2-benzyloxy-4- (1,1-di methylhexyl) -phenyl II cyclohexanol (3.0 g, 43%) and trans- isomer (660 mg of 9%) in the form of oils from 3-.2-benz1-1-4- (1,1-dimethylhexyl) -phenyl cyclohexanone (7.0 g, 17.9 mmol). The cis-isomer has an IR spectrum (SSCS): 3632, 3448, 1618 and 1575. Mass spectrum, m / e: 394 (M-). PMR, dcDCB3,: 0.82 (m, terminal methyl); 1.22 (s, heme-dimethyl); 3.07 (t, benzyl metin); 3.70 (t, Car bignol methine), 5.08 (s, benzyl methylene); 6.88 (dd, J 8 and 2 Hz, aromatic H)} 6.88 (d, J - 2 Hz, aromatic H), 7.12 (d, J - 8 Hz aromatic H) and 7.37 ( The bs, phenyl) trans-isomer has an IR spectrum (SSCS): 3623, 7448, 1618 and 1577 cm. Mass spectrum, m / e: 394 (Н). ITM nMP, O (; 0.80 (m, terminal methyl); 1.27 (s, heme-dimethyl), 3.42 (m, benzyl methine), 4.12 (t, carbinol-methine); 5, 02 (s, benzyl methylene); 6.83 (t, aromatic H) J 7.04 (d, J 8 Hz, aromatic H) and 7.34 (bs, aromatic H). P. cis-3-E2- Benzyloxy-4- (1,1-dimethylnonyl) -phenylZyclohexanol (5.0 g, 59%) and trans-isomer (1.0 g, 12%) in the form of oils from 3-C2-benzshloxy-4- (1, 1-dimethylnionyl) -phenyl cyclo. Hexanone (8.5 g, 19.6 mmol). The cis-isomer has an IR spectrum (CHCl3): 3623, 3448, 1618 and 1577 cm-T. Mass spectrum, m / e : 436 (M). PMR, OcDce Q, B3 (m, terminal methyl); 1.22 (s, heme-dimethyl); 3.04. (M, benzyl methine); 3.67 (m, heme-. dimethyl), 3.04 (m, benzyl methine); 3.67 (t, carbinol methine), 5.08 (s, benzyl methylene) 6.87 (dd, J 8 and 2 Hz, aromatic H), 6.87 (d, J 2 Hz, aromatic H) and 7.05-7.45 (t, aromatic H and phenyl), the trans-isomer has an IR spectrum (CHCl3): 3610, 3448, 1618 and 1575 cm. Mass spectrum, m / e: 436 ( n) .nMP,: 0.82 (t, terminal methyl), 1.22 (s, heme-dimethyl) 3.42 (t, benzyl methin); 4.16 (t, carbinol methin) 5.02 (s, benzyl methylene) and 6.7-7.5 (t, aromatic H and phenyl). R. cis-3- 2-Benzyloxy-l- (1,1-dimethylundecyl) -phene1 cyclohexanol (3.5 g, 50%) and the trans-isomer (1.0 g, 14%) as an oil from 3 C2 - 6-eonyloxy-4- (1,1-dimethylundecyl) -fensh1 of cyclohexanone (7.00 g, 15.0 mmol). The cis-isomer has an IR spectrum; 3636, 3448, 1621 and 1582 cm. Mass spectrum, m / e 464 (n). PMR, (: 0.95 (t, contra-methyl); 1.33 (s, hem-dimethyl); 3.09 (t, benzyl tin), 3.70 (t, carbinol methin), 5.20 (s, benzyl methylene); 6.99 (dd, J - 8 and 2 Hz, aromatic H); 6.99 (dd, J 8 and 2 Hz, aromatic H), 7.22 (d, J 8 Hz, aromatic H) and 7.50 (bs, phenyl H). The trans-isomer has an IR spectrum (SNSC): 3534 (wide), 1618 and 1577 cmL Mass spectrum, m / e: 464 (). PMR, (0 , 85 (jn, terminal methyl); 1.22 (s, heme-dimethyl); 3.48 (t, benzyl methine), 4.17 (t "benzyl metin) 5.08 (s, benzyl methylene) and 6 , 75-7.55 (t, arrmatic H and phenyl).
    C. cis-3-C 2 -Venzyloxy-.4- (1,1-dimethyldecyl) -phenylZcyclohexanol (2.66 g, 59%) and the trans-isomer (036 g, 8%) as an oil from 3-C2 -benzyloxy-4- (1,1-dimethyldecyl) -phenyl cyclohexanone (4.5 g; 10.0 mmol).
    The cis-isomer has an IR spectrum (CHCl j) of 3704, 3571, 1639 and 1597 cm
    Mass spectrum, M / ei 450 (M).
    PMR, (Gusyus% "0.86 (t, terminal
    methyl); 1.25 (s, heme-dimethyl), 3.08 (ffi, benzyl methine); 3.74 (t, carbinol methin) .; 5.08 (s, benzyl methylene), 6.88 (dd, J 8 and 2 Hz, aromatic H), 6.88 (d, J 2 Hz, aromatic H); 7.12 (d, J 8 Hz, aromatic H) and 7.37 (bs, phenyl),
    The trans-isomer has an IR spectrum (SSCS): 3623, 3448, 1616 and 1577 cm
    Mass spectrum, m / e: 450 (M).
    PMR, cg (J, 0.82 (t, terminal
    Kyutil), 1.22 (s, heme-dimethyl), 3.53 (t, benzyl metin); 4.22 (t, carbinol methyl); 5.02 (t, benzyl methylene) and 6.8-7.6 (t, aromatic H and phenyl).
    T. cis-3- 2-Benzipoxy-4- (1,1-Dimethylheptyl) -phenyl cyclooctanol (1.36 g, 19%) and the trans-isomer (4.12 g 59%) in oil from 3-12 -benzyloxy-4- (1,1-di vetilheptyl) -phenyl 3 cyclooctanone (7.0 g, 16.1 mmol).
    Mass spectra, m / e: 436 C), 421, 418, 351, 328., 243 and 91.
    PMR, (Tp-jj.g 0.83 (m, terminal
    methyl) 1.28 (s, heme-dimetnl); 3.4 (bra ,, benzyl metin); 3.9 (t, carbinol .metin) ;; 5.10 (s, beisyl methyl), 6.85 (t, aromatic H), 7.08 (d, J 8 Hz, aromatic H) and 7.36 (t, phenyl). .
    Example 11. (1,1-Dimethylheptyl) -2hexyphenyl-27Cylohexen yen. /,; -. .
    6.3 ml of 1 M (in toluene) are added dropwise to a solution of 1.00 g (3.19 mmol) (1,1-dimethyl-goptil) -2-hydroxyphenyl -2-cyclohexenone in 60 ml of ether. solution of diisobutylalanine hydride. The reaction mixture is stirred for 30 minutes at and then added to 1.5 liters of water. The stopped reaction mixture is extracted three times.
    400 ml of ether, mixed extracts. twice washed with 125 ml of saturated sodium chloride and dried over magnesium sulfate. After evaporation, the crude product is purified on a chromatographic column, eluting with ether, to give an oil. Crystallization of the oil from peitan gives 256 mg (25%) of the desired product, Ti mp. 87-88 C.
    Mass spectrum, m / e: 316 (M), 298, 231 and 213.
    PMR, SG.R: 0.83 (t, terminal
    methyl); 4.37 (t, metin carbinol); 5.90 ((IV, vinyl H) V 6.37 (b, OH) and 6.87 (t, aromatic H).
    Elemental analysis for C iCalculated,%: C 79.70, H 10.19.
    Found,%: C 79.68; H 9.96.
    Example 12 is cis-3-12-Benzyloxy-4- (1,1-dimethylheptyl) -phenyl3-trans-5-methylcyclohexanol and trans, cis-isomer. I: To a solution of trans-3-2-benzyloxy-4- (1 1-dimethylheptyl) -phenyl-5-methylcyclohexanone (300 mg, 10.714 kmol in 15 MP of methanol and 5 mp of tetrahydrofuran. Sodium borohydride (216 mg, 5.68 mmol) for 1 hour. The reaction mixture is stirred for 2 hours at -78 ° C, warmed to room temperature and evaporated under vacuum. The residue is acidified with dilute hydrochloric acid and extracted with ether. The extract is dried over magnesium sulfate and evaporated the residue is purified by chromatography on a column of 50 g with a "gelgel", eluted with a 30% mixture ether ether, resulting in the elution of 323 mg (77%) of trans, cis isomer and 45.9 mg (15%) of cis, trans isomer.
    trans, - cis-Isomer has a mass spectrum, m / e. - 422 (M), 337, 314, 220 and 91.
    imP, (f: 0.86 (n, trailing
    methyl); 1.05 (d, J - 7 Hz, C-5 methyl); 1.26 (s, heme-dimethyl); 3.70 (p, benzyl methin) 4.05 (p, carbinol methin), 5.13 (benzyl methylene); 6.8-7.0 (p, aromatic H) and 7.1-7.6 (p, aromatic H and phenyl).
    cis, - trans-I.zomer has a mass spectrum, m / e: 422 (M), 337, 314, 229, 206 and 91.
    PMR, (G7: 0.9 (n, terminal
    methyl); (d, J = 7 Hz, C-5 methyl); 3.1-4.3 (n, benzyl, carbinol methines); 5.13 (s, benzyl methylene); 5.40 (s, OH) and 6.8-7.7 (p, phenyl and aromatic H).
    Pr im ep 13. cis-3- 2-Benzyloxy-4- (1,1 dimethylheptyl) -phenyl 3-methyl-cyclohexanol and trans, trans-isomer.
    To the solution of cis-3-12-benzyl-4- (1,1-dimethylheptyl) -phenyl-3-5-methylcyclohexanone (228 mg, 0.543 mmol). in methanol (10 mp) at 78 ° C, sodium borohydride (150 mg, mmol) is added over 2 hours. The reaction mixture of the mixtures is heated to room temperature, and then
    Sodium laureate is added to our brine solution and then extracted with ether. The ether extract is dried over magnesium sulphate and evaporated under reduced pressure. The stalk is cleaned on a preparative chromatographic layer on five silica gel plates 20 cm x 20 cm x X0.5 mm, eluted by a 50% ether-pentane mixture, to obtain 36 mg (16%) trans, - trans-isomer (Rj 0.25 , silica gel, 33% ether-pentrole ether) and 168 Mg (R 0.17, silica gel, 33% ether-petroleum ether) cis, dis-isomer. :
    Example 141 cis-3-4- (1,1-dimethylhepton) -2-hydroxyphenyl-cis-5-methylcyclohexanol. Sodium borohydride (805 mg, 21.8 mmol) was added to a solution of cis-3- 4- (1,1-dimethylheptyl) -2-hydroxyphenyl-5-methylhexanone (896 mg, 2.13 mmol) in 30 ml of methanol. ). The reaction mixture is stirred for 1 h at, warmed to room temperature and added to ether and saturated sodium chloride. The ether extract is dried over magnesium sulphate and evaporated to give an oil. Crystallization from peitan yields 589 mg (65%) of the title compound, m.p. 113-114c.
    IR spectrum (CHCl3): 3636, 1390, 1681 and 1592 cm.
    Mass spectrum, m / e: 332 (M), 314, 247, 229 and 95.
    nMP, ((m, C-5 and end
    methyl): 1.21 (s, heme-dimethyl); 2.95 (p, benzyl metinU; 3.82 (p, metin carbinol) 5.62 (s. OH) 6.82 (p, aromatic H) and 7.12 (d J 8 Hz, aromatic H).
    Elemental Aneshie Dl .:
    Calculated,% C 79.46; H 10.81.
    Found,%: C 79.79, H 10.62.
    Similarly, the following compounds can be obtained.
    A. cis-3- 4- (1,1-dimethylheptyl) 2-hydroxyphenyl-cis-5-ethylcyclohexanol (0.74 g, 74%) from cis-3-C4- (1,1-dimethylheptyl) -2- hydroxyphenyl 5-ethylcyclohexanone (1.00 g, 2.30 mmol). T. pl. llO-lll C.
    Their spectrum (SNSC): 3636, 3367. 1631 and 1587 cm-H.
    PMR, SG: 0.90 (p, trailing
    methyls); 1.22 (s, heme-dimethyl) 2.95 (n, benzyl methine); 3.85 (p, metin carbinol); 5.59 (s, .OH), 6.85 (p, aromatic H) and 7.10 (d, J - 8 Hz, aromatic H).
    Elemental analysis for Cjifl ipi t Calculated,% 1 C 79.71; H 11.05, Found,%: C 79.41; H 10.71. B. cis-3-C4- (1,1-Dimethylheptyl) g 2-hydroxyphenyl 3 -cis-5-n-propyl cyclohexanol (0.954 g, TIfV nz cis-3-C 4- (1,1-dimethylheptyl) -2-hydroxyphenyl 5 -5-n-propylcyclohexanoia (1.34 g,
    3.74 mmol). T. pl. 103-104 C (from pentane).
    IR spectrum (sleep C): 3636, 3378, 5 1626 and 1587 CM-l
    Mass spectrum, M / e: 360 (m), 342, 275, 257 and 161.
    PMR, 0.90 (n, the end
    l methyls); 1.22 (s, heme-dimethyl); 2.95 (p, benzyl metin); (s, metin carbinol); 5.42 (s, OH) / 6.85 (p, aromatic H) and 7.08 (d, J
    -8 Hz, aromatic H).
    Elemental analysis for Ci, ii
    five
    Calculated% 1 C 7.9.94; H 11.19.
    Found,%: C 79.88, - H.11.22.
    B. cis-3-.4- (1,1-Dimethylheptyl) -2-hydroxyphenylZ-cis-5-n-hexylcyclohexanol from cis-3-14- (1,1-dimethylhep0-tyl) -2-hydroxyphenyl 3-5- n-hexencyclohexanone (1.20 g, 3.00 mmol) by chromatography on 120 g of silica gel eluted with a 50% ether-pentane mixture, in quantitative yield in the form of 5 masps containing traces of trance, trans-isomer.
    IR spectra (SNRC): 3623, 3355, 1626 and 1585 cm-1
    Mass spectrum, m / e: 402 (m), 384, 0 317 and 299.
    PMR, (f J o f 90 (n, terminal
    . methyls); 1.22 (s, heme-dimethyl); 2.97
    (m, benzyl metin); 3.85 (p, metine carbinol), 4.32 (p, metin carbinol trais, trans isomer), 5.58 (bs, OH) 6.85 (p, aromatic H) and 7.09 (d , J “8 Hz, aromatic I).
    The analgesic properties of the compounds according to the invention are determined by tests using iociceptive stimuli.
    1. Tests using thermal nociceptive stimuli.
    a) Analgesic testing with a hot plate (H1.
    The method used is a modification of the Wulff MacDonald method. Adjustable thermal stimulus acts on the legs of the side of the aluminum plate with a thickness of 3 mm. A 250-watt infrared reflector heater is placed under the bottom of the alumina plate. A thermal regulator connected to a thermistor on the plate surface is programmed to maintain a constant temperature (). Every mile is placed in glass .nny cylinder
    150 mm in diameter, standing on a hot plate and mark the time when the animal's feet touch the plate. The mouse is observed after 0.5 h and 2 h after the treatment with the following u. by connecting up to the appearance of the first building movements of one or both hind legs, or until 10 seconds have passed without the occurrence of such movements. Morphine has the maximum possible effect of 4-5.5 mg / kg (subcutaneously).
    b) Analgesic test with the withdrawal of the mouse tail (TF).
    Tail rejection in mice is a modification of the method of d'Amour and Smith using high-intensity heat applied to the tail. Each mouse is placed in a precisely fitted metal cylinder so that the tail sticks out from one end. This cylinder is installed in such a way that the tail lies flat on top of the hidden heat lamp. At the beginning of the test, the aluminum flag above the lamp is removed, allowing the light to pass through the slit and focus on the end of the tail. At the same time start the stopwatch. The lag time of the sharp tail retraction is determined. Untreated thoughts usually respond within 3–4 s after the onset of exposure to the lamp. The limit for the defense reaction is 10 s. Each mouse is tested at 0.5 hours and 2 hours after treatment with morphine and the test compound. Morphine has the maximum possible effect of 3.2–5.6 mg / kg (subcutaneously
    n) Method with immersion tail.
    The method is a modification of the cluster method developed by Venbass. Male white mice (19-21 g) of the strain of -Charles River CD-I are weighed and labeled for identification. Usually, five animals are used in each group treated with the drug, each animal serving as a control for itself. For general screening purposes, new test substances are first administered at a dose of 56 mg / kg intraperitoneally or subcutaneously with a volume of 10 ml / kg. Before drug treatment and after 0.5 h and 2 h after drug administration, each animal is placed in a cylinder. Each cylinder is provided with openings to provide adequate ventilation and is closed with a round nylon stopper through which the tail of the animal is drawn.
    The cylinder is supported in. position and tail fully immersed in a constant-temperature water bath (). The end point for each experiment is an energetic jerk or jerking effort of the tail associated with a motor reaction. In some cases, after medication, the end may be less vigorous. In order to prevent undesirable damage to the tissue, the experiment was stopped and the powder was removed from the water bath after 10 s. The reaction time lag is recorded in seconds with an accuracy of 0.5. The control medium and the standard are tested with the selected candidates with a known effect. If the activity of the test agent is not returned to the background level when tested after two hours, then the reaction lag is determined after 4 hours and b.h. The final measurement is made 24 hours later if activity is still observed at the end of the day of the test. I
    2. Test using chemical nociceptive stimuli.
    Suppression of convulsions caused by phenylbenzoquinone irritant (PBQ).
    Groups of 5 -mute Carworth Farms CF-1 strain are pretreated subcutaneously or orally with saline, morphine, codeine, or test compound. After 20 mi (during treatment) or after 5–10 min (during oral treatment) phenylbenzoquinone (a known irritant, causing peritoneum contraction) is intraperitoneally injected into the group. Mice are observed for 5 min for the presence or absence of convulsions, starting after 5 min after the injection of irritant. Estimate the relic of the maximum possible effect of MV% (5 pre-administered agents for convulsions).
    3. Tests using mechanical nociceptive stimuli.
    Tail Restraint Method (PCT), which is a modification of Gaffner's method for assessing the effectiveness of a test compound by the aggressive attack reaction caused by a stimulus that restrains the tail. Male white rats (50-60 g) of Charles River strain are used. Before medicinal treatment, as well as after 0.5 J 1.2 and 3 hours, after treatment with a 2.5-inch bulldog Jones-Hopkins clamp, the root of the rat tail is clamped. The end point of each experiment is a clear attacker and a piece of behavior that is directed against the offended one of the irritants, and the reaction time lag is recorded in seconds. The clamp is removed after 30 seconds if the attack has not yet followed, and the reaction lag is recorded as 30 seconds. Morphine has activity at 17.8 mg / kg (intramuscularly).
    4. Tests using electrical nociceptive stimuli.
    To determine the pain thresholds, use is made of a modification of the jump start mode — Jump Shadow (Ff). Male white rats (175-200 g) of the Psychophermacolody strain are used. Perel
    taking the medicine each rat's feet is dipped in 20% glycerin (saline). The animals are then placed in xaMejpy and exposed to a sequence of 1-second electric shocks, which are served with increasing intensity at 30-second intervals. These intensities are 0.26; 0.39; 0.52 / 0.78; 1.05; 1.31} 1.58; 1.86, 2, 42, 2.72 and 3.04 mA. The behavior of each animal is evaluated for the presence of agivania, squeaking, and sub {xdgivani or
    experimental time - control time
    % IVE termination time - control time
    The proposed compounds used as analgesics for oral or parenteral administration are usually administered in the form of a composition. l Such compositions include a pharmaceutical carrier selected on the basis of the chosen route of administration and
    fast forward at the moment of impact. In one incremental sequence, electric shocks are applied to each rat before and after 0.5; 2; 4 and 24.h after it
    The test results are recorded as a percentage of the maximum possible effect (% MBE), which in each group is statistically compared with the standard and control values before the administration of the drug. % KVE calculated in the following way:
    X 100
    conventional pharmaceutical practice. For example, they can be administered in the form of tablets, pills, powders or granules.
    The analgesic activity of some of the above compounds is presented in the table.
    权利要求:
    Claims (3)
    [1]
    Invention Formula
    The method of obtaining 3- (2-hydroxy-4-substituted-phenyl) -cycloalkanol compounds of the general formula
    AND HE
    Z-W
    de r. - hydrogen or benzyl,
    RJ is hydrogen, alkyl, alkenyl C,
    R, is hydrogen, methylJ
    RJ is hydrogen, alkyl.
    alkylene, (alkyl Z-0- {alkyl 2) and, where each alkyl 1 and 2 is alkylene Cjf-C -, provided that the total number of carbon atoms in (alkyl) and (alkyl) does not exceed 13; 0.1;
    // V,
    W is hydrogen or
    where W is hydrogen, fluorine, chlorine;
    n - O, 1, 2, 3, provided that R is hydrogen, then n - O and dotted lines indicate the presence of a double bond in one of the indicated j. places that
    distinguished by the fact that the carbonyl compound of the general formula
    ABOUT
    OR,
    (SNg) C
    Z-W
    where, 2, W, p have the indicated
    5 values
    reduced with an alkali metal borohydride or diisobutylaluminum hydride in an organic solvent at a temperature of from -78 to
    0 EPA.
    Sources of information taken into account in the examination
    li M chkovskip M, D, Medicinal products, t, 1 ,. M., Medicine, 197.7, p. 160-161, 147.
    five
    [2]
    2. US patent 3379770, cl. 260-611, published. 1968. i
    [3]
    3. The patent of ODA 3480571, cl. 260-617, published. 1965.
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US83310277A| true| 1977-09-13|1977-09-13|
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