M. Rajkovic

New Types of Steroidal Isoxazolidines

Synthese de 1β,5- et 3β,5- epoxyimino steroides a partir de N-methyl hydroxylamine et de 5,10-secosteroides

Oxidative β -fragmentation of 19-nor-5α-androstane-3β, 5, 17β-triol 3, 17-diacetate

Abstract The preparation of 19-nor-5α-androstane 3β,5, 17β-triol 3,17 diacetate (10) is described. When this alcohol was treated with the mercuric oxide-iodine reagent it underwent fragmentation of the C(5)–C(10) bond with formation of a new type of 10-membered ring containing 5,10-seco-steroidal compounds, i.e. (Z)-and (E)-19-nor- 3β, 17β diacetoxy-5,10-seco-androst-1(10)-en-5-one (11 and 12), in 27 and 49% yield, respectively.

Structure-reactivity relationship in 19-methyl-and 19-nor-5,10-secosteroids. Part 4. Intramolecular nitrone 1,3-dipolar cycloadditions

The (Z)-19-nor-5,10-secosteroidal ketone 11 reacts with hydroxylamine hydrochloride to give the (E)- and (Z)-oximes 12 and 13, while with N-methylhydroxylamine hydrochloride it undergoes transannular nitrone 1,3-dipolar cycloaddition to give isoxazolidines 14 and 15, and an estratriene derivative 16, originating from 14. The (E)-19-nor-5,10-seco-ketone 17 undergoes intramolecular nitrone 1,3-dipolar cycloaddition with both hydroxylamine hydrochloride and N-methylhydroxylamine hydrochloride to produce, with the former reagent, a single isoxazolidine 18, and with the latter, two regioisomers 22 and 23. The reaction and stereochemical courses of the above transformations are compared with those previously observed for the corresponding 19-methyl analogues. Copyright (C) 1996 Published by Elsevier Science Ltd.

Structure–reactivity relationships in normal and 19-nor-5,10-seco-steroidal cyclodecenone systems. Part 1. Acid-catalyzed and thermal reactions

Under acid-catalyzed conditions both the (Z)- and (E)-19-nor-seco ketones (1a) and (2a) underwent transannular cyclization [forming the C(5)–C(10) bond], accompanied by aromatization of the resulting ring A, to give estra-1,3,5(10)-trien-17β-yl acetate (4)(in 76% and 83% yield, respectively). On the other hand, when the corresponding 19-methyl analogues (1b) and (2b) were treated with acid under similar experimental conditions, the (Z)-diastereoisomer (1b) remained mostly unchanged, while the (E)-19-methyl-seco ketone (2b) afforded the A-nor-B-homo derivative (5)(in 68% yield). The same transannular cyclization of the (E)-seco ketone (2b) was also achieved thermally in the absence of protonation.

Oxidative hydrolysis and acid-catalyzed rearrangement of steroidal isoxazolidines

Abstract Treatment of steroidal isoxazolidines 3a, 3b and 5b with N-methylhydroxylamine hydrochloride in boiling ethanol-pyridine (1:1) solution results in elimination of the CH 3 NH 2 fragment, affording products of oxidative hydrolysis 4a, 4b, and 6b, while acid-catalyzed reaction of isoxazolidines 2a, 3a and 5b leads to rearrangement involving the N-CH 3 group with formation of the perhydro-3,1-oxazine derivatives 8a, 9a and 10b .

Acid-catalyzed rearrangement of some steroidal isoxazolidines

Abstract Acid-catalyzed reaction of the steroidal Δ1-unsaturated 3β,5β-epoxyimino compound 2 and Δ3-unsaturated 1β,5β-epoxyimino products 3 and 7, results in intramolecular rearrangement involving the N-CH3 group to give the corresponding perhydro-3,1-oxazine derivatives 9–11. Under similar reaction conditions, the saturated analogues 4, 6 and 8 remain unchanged. The difference in reactivity between the unsaturated and saturated compounds is studied and elucidated by the semiempirical molecular orbital MNDO-PM3 method.