Elsevier

Steroids

Volume 6, Issue 6, December 1965, Pages 805-840
Steroids

Steroids and related products. XXIV. The synthesis of 17α-amino 20-keto steroids. Part I☆,☆☆

https://doi.org/10.1016/0039-128X(65)90102-9Get rights and content

Abstract

The first synthesis of 17α-amino derivatives of 3, 20-dioxygenated pregnanes is described. Thus, 17α-amino-3α, 16α-dihydroxy-5β-pregnane-11, 20-dione and 17α-amino-3α, 11β, 20ξ-trihydroxy-5β-pregnane and some of their acetyl and sulfonyl derivatives were prepared from 3α-acetoxy-5β-pregnane-11, 20-dione. The introduction of the nitrogen function was effected through the opening of the epoxide function of a 16, 17β-epoxy 20-oxo 17-isopregnane with sodium or lithium azide. The reaction products isolated after working up in the presence of sodium hydroxide had the 16α,17α cis configuration, as evidenced by the facile acetyl migration during reduction of the 16-acetoxy 17-azido derivative and by the ready formation of an oxazoline in the course of Raney nickel reduction of this 16-acetoxy 17-azide. The formation of a cis hydroxy azide is rationalized by epimerisation of the 16-hydroxy function of the product initially formed by a transquasi-diaxial opening of the epoxide. The conversion of the azide function to the amino function was achieved either by catalytic reduction or by reduction with lithium aluminum hydride. The oxygen function in position 16 was removed by metal hydride reduction of the corresponding tosylate. The experiments described represent a general pathway towards the synthesis of 17α-amino analogues of steroid hormones of the progesterone-corticoid group.

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    ☆

    For a preliminary report of this work see: Abstracts of communications, 2nd Int. Symposium on The Cheistry of Nnatural Products, Prague, 1962, p. 130.

    ☆☆

    Visiting Professor, Laval University, 1960–1962. Present address: Ecole Nationale Supérieure de Chimie, Université de Montpellier, Montpellier, France.

    3

    Paper XXII of this series: Engel, Ch.R. and Bach, G. Steroids, 3, 593 (1964).

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