Steroids and related products. LIII. The synthesis of 11-oxa steroids. V. The synthesis of 17-ethynyl-11-oxatestosterone

The synthesis of 17-ethynyl-11-oxatestosterone, both from 11-oxa-5 alpha-pregnane-3,20-dione and, via a 3,17-dioxygenated 9-oxo 9,12-seco 11-nor 5 alpha-androstane-12-oic ester, from 3 beta-acetoxy-17-hydroxy-5 alpha-pregnan-12-one--two products available from hecogenin--is reported. The new hormone analogue shows significant progestational activity in the Clauberg test and relatively weak activity in a post-coital antifertility assay.     

Steroids and related products. XLI. (1) the synthesis of 11-oxa steroids. III. (2) 17-acetoxy-11-oxaprogesterone (3).

The synthesis of 17-acetoxy-11-oxaprogesterone, the 11-oxa analogue of the orally active progestational and anti-fertility agent 17-acetoxyprogesterone, is described. An intermediate in the synthesis of 11-oxaprogesterone, 11-oxa-5alpha-pregnane-3,20-dione, available from hecogenin, was used as starting material and the 17-hydroxy function was introduced by a modified Barton oxidation. The new hormone analogue shows only extremely weak progestational activity in the oral Clauberg assay.     

Steroids and related products. 38. 11-Aza steroids. 3. The synthesis of 11-aza 9 -steroids. I

The synthesis of 3,20-dioxygenated 11-azapregnanes, with a “normal” (a) configuration.in position 9, is described. The saturation of the 8,9-double bond of previously described unsaturated precursors can be effected not only by reduction of 9,11-iminium salts, but also catalytically, under pressure, in the presence of perchloric acid, It is shown that the 7-position of 8,9-unsaturated 11-aza steroids can be functionalized with the chromic acid-pyridine complex, the double bond of the resulting 7-ketone being prone to Birch reduction. Other, direct, pathways from saturated 11-nor 9,12-seco steroids to saturated 11-aza 9α-steroids have been explored. The crucial difficulty inherent in this approach stems from the fact that in displacement reactions involving an axial 9α-substituent, elimination competes successfully with substitution.     

Steroids and related products. L. The synthesis of 17-methoxymethylprogesterone

A new progesterone analogue, 17-methoxymethylprogesterone, was synthesized from pregnenolone by two pathways, one involving as intermediate a 17-hydroxymethylated adduct, the other one by methoxymethylation of a 17,20-lithium enolate with bromomethoxymethane. The product shows significant progestational activity.     

Steroids and related products. XLVII. Cardiotonic steroids. VII. The 14β-hydroxylation of 17β-substituted steroids. Part II

The most efficient method for introducing a 14β-hydroxy group into a steroid with a 17β-side chain is reported. It can be used in the presence of an unsaturated lactone ring.     

Steroids and related products. XLVI. The regiospecific alpha-hydroxymethylation of saturated carbonyl compounds via preformed enolate ions. An improved synthesis of 17-hdyroxymethyl 20-keto steroids

As demonstrated for pregnenolone, saturated ketones are conveniently alpha-hydroxymethylated by their transformation into a lithium enolate and by the reaction of the latter with formaldehydr. The 17-hydroxymethylpregnenolone prepared by this method in very good yield was readily converted to 17-hydroxymethylprogesterone; either by selective acetylation in position 17(1) and subsequent Jones oxidation, followed by hydrolysis, or by conversion to the 4,5-dibromo 3-ketone - by bis(tri-n-butyltin)oxide-bromine oxidation or by dibromination and oxidation with N-bromoacetamde - and debromination with zinc and acetic acid.     

Steroids and related products. 39. The functionalization of the 17-methyl group of 17 -methyl steroids. II. The synthesis of 12 ,17 1 -epoxy-17 -methylprogesterone and of 20-oxygenated 17 -hydroxymethyl steroids

The functionalization of the 17-methyl group of 17α-methylated 20-oxygenated steroids is reported. Two methods were employed for that purpose: the Jeger reaction with lead tetraacetate, applied to a 12α-hydroxy 17α-methyletianic ester, leading to a 12,17¹-epoxide and the photolytic Barton reaction, applied to the corresponding 12-nitrite, and leading to a 17¹-nitroso derivative which was transformed into a 17β-methoxycarbonyl lactone of a 12α-hydroxy 17α-etianic acid. The 17β-ester group of this compound can be selectively hydrolyzed and the lactone group can be reduced to a 12α-hydroxy 17α-hydroxymethyl steroid. The synthesis of 12,17¹-epoxy-17α-methylprogesterone is also described.     

Efficient synthesis of C-11 functionalized steroids

An efficient synthesis from readily available materials of numerous steroids functionalized at C-11 position, interesting from a biological point of view, is described using our general approach. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized steroids are reported.     

19-hydroxy steroids. VI. Approaches to the synthesis of 7,19-disubstituted androgens

For the purpose of identification of 7-substituted Δ⁵-Steroids some compounds were prepared via stereospecific reactions and their molecular rotations and pertinent nuclear magnetic resonance data were correlated. Other approaches for the stereospecific introduction of 7-substituents into Δ⁵-Steroids were investigated.     

Stereoselective synthesis of pentacyclic steroids functionalized at C-11

We set out to describe an efficient and versatile method for preparing pentacyclic steroids diversely substituted at C-11 from cholic acid, via a stereoselective epoxidation and the epoxide opening as the key steps. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized compounds are reported.     

Microbial transformation of steroids XIX. Transformation of Steroids byMycobacterium flavum

при изучении τранс0444;ормируюшей спообосτи шτамма Μусоьасегm ?аνm № 390 по отмошемию к стероидам андросτенового ряа (E⁴‐андросτен–з, 17‐диону и τес τосτерону) было доказано возниKкновеение соответствующих 1-дегидропроизводннх. Дегидрироввние в положении 1—2 сопровоаждеτся, од;‐ како,одновременн оокислиτельно‐вос‐ сτановиτельнымпро Цессом в полже – нии С₁₇. сτероидов п регненооого ряда, Υ коτорыхв положении С₁₇неτ окси – группы (прогесτерон, его 20β– окси– произвдное, 11–дезоксикорτикос τерон), в каЧесτве первиЧной реакции происхо– диτ оτЩпление боковой цепи, приЧем возникаеτ△⁴‐андро сτен‐ 3,17‐дион.По– следуыЩей реакцией являеτся поτом дегидрирование в положеоии 1—2, со– провождаыЩееся окислиτеьновоссτа-нвовиτелнымпр оцессомвположении С₁₇. Υ сτероидов нрегненового рада с осигруппой вположении 17_α(сτе‐ роид ?S?, корτизон, преднизон)ни в одном случае не происходиτ оτшепле– ниябоковй Цепи в положении С17. в качестве первнчной реакции протекаем дегиирирование в положении1—2. возникающее макин обрабон l-де гидропронзвоSдное восснанавливается, однако, далеев поожеоии С₂₀ в сооτвеτсτвую– шее 20 β ‐ окси ‐l‐-д егидропроизводное ис‐ ходного сτероида. пра продлении пе – риода ферменτаЦии (на 48 часов)Цре ‐ враmение проЦ олжаеτся Цалее при об ‐ разованииявноне сτероиЦных меτабо — лиτов.     

The regulation of haemoglobin synthesis in cultured chick blastoderms by steroids related to 5beta-androstane.

1. After 24h of incubation, the blastoderm may be dissected from the early developing chick embryo and successfully maintained under conditions of organ culture in vitro. 2. Low concentrations of steroids related to 5beta-androstane stimulate the synthesis of foetal haemoglobins, types E and P, in a highly steroid- and tissue-specific manner.