HCID 15125796, compound → 120185-34-4

HRID 1492095Notes

Reaction equation

[OH:1]CC(=CCC[C@H]([C@@H]1[C@]2(C)C(=C3[C@H](CC2)[C@]2(C)[C@H](CCCC2)CC3)C(=O)C1)C)C.C([O:33][C@H:34]1[CH2:58][CH2:57][C@@:56]2([CH3:59])[C@@H:36]([CH2:37][CH2:38][C:39]3[C@@H:55]2[CH2:54][CH2:53][C@@:52]2([CH3:60])[C:40]=3[C:41](=[O:61])[CH2:42][C@@H:43]2[C@H:44]([CH3:51])[CH2:45][CH2:46][CH:47]=[C:48]([CH3:50])[CH3:49])[CH2:35]1)(=O)C>>[OH:33][C@H:34]1[CH2:58][CH2:57][C@@:56]2([CH3:59])[C@@H:36]([CH2:37][CH2:38][C:39]3[C@@H:55]2[CH2:54][CH2:53][C@@:52]2([CH3:60])[C:40]=3[C:41](=[O:61])[CH2:42][C@@H:43]2[C@H:44]([CH3:51])[CH2:45][CH2:46][CH:47]([OH:1])[CH:48]([CH3:50])[CH3:49])[CH2:35]1.[OH:33][C@H:34]1[CH2:58][CH2:57][C@@:56]2([CH3:59])[C@@H:36]([CH2:37][CH2:38][C:39]3[C@@H:55]2[CH2:54][CH2:53][C@@:52]2([CH3:60])[C:40]=3[C:41](=[O:61])[CH2:42][C@@H:43]2[C@H:44]([CH3:51])[CH2:45][CH2:46][CH2:47][C:48]([OH:1])([CH3:49])[CH3:50])[CH2:35]1

Participants

Reactant 2

HCID 15125796HCID 15125796, compound

HCID 86748299HCID 86748299, compound

Product 2

HCID 15125800120185-34-4

HCID 152313003,24-Dihydroxycholest-8(14)-en-15-one

Procedure

The synthetic protocols to be followed for preparing the preferred side chain derivatized cholest-8(14)-en-15-one compounds are known to those of skill in the art. For example, 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one is converted to 3β-acetoxy-15-keto-5α-chol-8(14)-en-24-oic acid by oxidation of the alcohol with Jones reagent and subsequent hydrolysis of the C-3 acetate. Compounds such as 3β,24-dihydroxy-5α-cholest-8(14)-en-15-one, 3β,25-dihydroxy-5α-cholest-8(14)-en-15-one and 3β-hydroxy-5α-cholesta-8(14),24-dien-15-one arise from a common intermiediate, viz., 3β-acetoxy-15-keto-5α-chol-8(14)en-24-al. The C-24 aldehyde is readily prepared from 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one by oxidation with periodinane according to the method of Dess and Martin. Wittig olefination of 3β-acetoxy-15-keto-5α-chol-8(14)en-24-al yields a 24-olefin, 3β-acetoxy-5α-cholesta-8(14),24-dien-15-one which may be hydrolyzed to 362 -hydroxy-5α-cholesta-8(14),24-dien-15-one. Hydration of the 3β-acetoxy-5α-cholesta-8(14),24-dien-15-one and hydrolysis of the ester yields either 3β,24-dihydroxy-5α -cholest-8(14)-en-15-one or 3β,25-dihydroxy-5α-cholest-8(14)-en-15-one, depending upon the reaction conditions selected. For example, oxymercuration of the 24-olefin will result in 3β,25-dihydroxy-5α-cholest-8(14)-en-15-one, while hydroboration will give 3β,24-dihydroxy-5α-cholest-8(14)-en-15-one. The 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one is converted to 3β-acetoxy-5α-chola-8(14),23-dien-15-one by treatment with ortho-nitrophenyl selenocyanate, followed by hydrogen peroxide. Reaction of this 23-olefin with 2-iodoheptafluoropropane produces 3β-acetoxy-23ξ-iodo-25,26,26,26,27,27,27-heptafluoro-5α-cholest-8(14)-en-15-one. Subsequent reduction with tributyl tin hydride and deprotection of the C-3 alcohol yields the F7 analog of the starting sterol, viz., 3β-hydroxy-25,26,26,26,27,27,27-heptafluoro-5α-cholest-8(14)-en-15-one. Alternatively, the free hydroxy in 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one may be converted to a leaving group and replaced by nucleophilic substitution. Transformation of 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one to the C-24 tosylate followed by reaction with dimethylamine and saponification gives the 25-aza analog of the cholest-8(14)-en-15-one, 3β-hydroxy-24-dimethylamino-5α-cholest-8(14)-en-15-one.

Sources & evidence

ORD record: ord-cb442090bc634364bc8a0ad3495a9073
Source dataset: uspto-grants-1994_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05371077

Reaction notes

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