Amino-steroids. Part 6. Stereospecific syntheses of eight, isomeric, steroidal vicinal 2,3-amino-alcohols

Abstract

The seven possible 3-amino-2-hydroxy and 2-amino-3-hydroxy isomers of the anti-arrhythmic steroid, 3a-amino-2P-hydroxy-5a-androstan-1 -/-one, were prepared from 5a-androst-2-en-17-one. The intermediate 2a,3a-and 2@,3P-epoxides and aziridines were cleaved to vicinal frans-diaxial amino-and azido-alcohols, which in turn yielded the isomers by a series of functional group inversions and transformations.* An alternative route to the aziridine (30) involved reaction of (25) with p-nitrophenylsulphonyloxyurethane and triethylamine, leading t o the N-ethoxycarbonylaziridine (3 1) which was converted into (30) by potassium hydroxide in ethanol.* Photochemical ring-expansions were unsuccessful, and it is of interest that thermolysis led only to the oxazoline (59), none of the alternative 2p,Sp-isomer being isolated.

New Structure–Activity Relationships of A- and D-Ring Modified Steroidal Aromatase Inhibitors: Design, Synthesis, and Biochemical Evaluation

“…Treatment of 14 with performic acid in dichloromethane led to the epoxide derivative 15 , in 96% yield (Scheme ) . The 2,3-epoxide 17 was synthesized from the commercially available 2,3-olefin 16 by two different pathways: via performic acid, Method A, and via peracetic acid, Method B . As the starting material 16 was only available in 92% purity (it is supplied in a 92:8 inseparable mixture with 14 ), the resulting compound 17 was also obtained in 92% purity (NMR and HPLC analysis) (Scheme ), by both methods.…”

Steroidal Conjugates and Their Pharmacological Applications

“…13) (Am, 3 -amino-2 -hydroxy-5 -androstan-17-one) possessed interesting antiarrhythmic activity in animal models [81] and was developed to the stage of clinical testing, but did not become commercially available because it was deemed not to have sufficient oral bioavailability [82]. In China, Fang and co-workers [83], in an attempt to develop aminosteroid derivatives with more desirable antiarrythmic properties, prepared a number of amide and N-alkyl derivatives of amafalone.…”

Phase-Transfer-Catalyzed Oxidations

“…The PTe method is a preferred technique for permanganate hydroxylation of olefins to cis-diols [32][33][34]. For example, with cyclooctene [35]:…”