Pregnane derivatives

The addition proceeds most smoothly with highly functionalized (more polar) steroids as seen in examples by Bernstein and others. The polar reaction conditions pose solubility problems for lipophilic androstane, cholestane and pregnane derivatives. Improved yields can be obtained in some cases by using dimethyl sulfoxide or t-butanol " as solvents and by using sodium A-bromobenzenesulfonamide or l,3-dibromo-5,5-dimethyl hydantoin (available from Arapahoe Chemicals) as a source of positive bromine. The addition of bromo acetate and bromo formate to steroid olefins has been studied to a limited extent. ... 

Expansions of oximes of B-ring steroid systems are much less common. Recently, during the synthesis of a 6-aza-pregnane derivative 387, the introduction of the nitrogen was made using the Beckmann rearrangement reaction (equation 156). 

The application of Westphalen and backbone rearrangement reaction conditions (MeN02, Bi(0Tf)3xH20 catalyst) [118] to 16a,17a-epoxy-20-oxosteroids has also been studied [124]. At room temperature and 0.05 eq. of catalyst, low conversion of 16a,17a-epoxy-20-oxopregn-5-en-3p-yl acetate was observed. However, on increasing the temperature to 50 °C, 16a- and 16p-hydroxy-17p-methyl-A13-18-nor pregnane derivatives were formed in near similar amounts from 16a,17a-epoxy-20-oxosteroids (Scheme 33). 

It has been reported that the reaction of NN-dimethylfuntumine (la) with trichloroethoxycarbonyl chloride gave the elimination product (2), in high yield, rather than the expected urethane (lb).4 Under the same reaction conditions the epimeric dimethylamino-pregnane derivatives (3a) and (3b) both gave the olefin (4), accompanied by minor amounts of the expected urethanes (3c) and (3d) respectively. The reaction of conessine (5a) with Cl3CCH2OCOCl yielded only the urethane (5b).4... 

Acid-catalysed hydrolysis of the carbamate (15a)14 gave the amino-pregnane (15b).15 The latter amine underwent a condensation reaction with 3,5-di-t-butyl-o-quinone to yield an anil which gave progesterone (15c) on hydrolysis with an acetate buffer.16 Other amino-pregnane derivatives have been prepared by degradation of solasodine17 (vide infra). 

Phenyl ketones (201), readily prepared from compounds with cholanic acid or lanosterol side chains, are degraded in alkaline solution by molecular oxygen, giving bisnorcholanic acids (202). Decarboxylation with lead tetra-acetate in benzene, with a little pyridine, completed the degradation to a pregnane derivative, giving the mixed 20-acetates (203) with overall yields in the range 30—40% for the two steps.177... 

Lindemann, P and Luckner, M. (1997) Biosynthesis of pregnane derivatives in somatic embryos of Digitalis lanata. Phytochemistry, 46, 507-13. 

A group of reactions involving 16,17-epoxy-pregnane derivatives illustrates the facility of C(is) methyl migration to an electron deficient C(i ). The i6a,i7a-epoxypregnan-20-ones (13) react with acetic anhydride and toluene- -sulphonic acid [24], hydrogen fluoride [23], and other acidic reagents [23,26], to form i7a-acetyl-i7/5f-methyl-i8-nor-olefins (14) and (15). The preferred position of the double bond apparently... 

The use of anisoles (22) as synthetic equivalents to cyclohex-2-enones (Scheme 3) has been widespread since the original observations of Birch, and the literature is replete with examples over the past five decades, e.g. in the syntheses of steroids, terpenoids and alkaloids. The most thorough studies have been carried out within the context of the conversion of estrone derivatives to 19-norandrostane and pregnane derivatives and are instructive for the selection of reagents and reaction parameters for reductions of this general type. ... 

A number of other synthetic approaches to the steroid skeleton are discussed in the following sections, which are devoted more specifically to the synthesis of oestrane, androstane, and pregnane derivatives, as well as to seco-compounds and steroidal alkaloids. 

From the pregnane derivative 46 in alcohol, 21-alkoxy-16,17-monooxirane and a little bisoxirane 47 are produced (Eq. 20) more 47 is formed in dioxan. ... 

The steroidal alkaloids have a nucleus based on 21, 24, or 27 carbon atoms (Fig. 44). The C21 alkaloids are pregnane-derived with nitrogen inserted at C-3, at C-20, or at both positions. They are characteristic of the Apocynaceae Funtumia and Holarrhena species) and the Buxaceae Buxus species). The Buxaceae also produces C24 alkaloids based on the cycloartane skeleton. The most interesting alkaloids are those in the Solanaceae and the Liliaceae. These are C27 alkaloids, and examples include solasodine and solanidine many derivatives are glycosylated. The alkaloids from the Liliaceae, such as veratramine of the white hellebore (Veratrum album), were formerly used for cardiac... 

Relative retention time (RRt) is defined as the ratio of the analyte and the reference compound s retentions. The RRt of sterols relative to cholesterol and cholestane, stearyl acetates to cholesteryl acetate, estrogen derivatives to cholestane, estrogen TMS ether to cholestane on various packed columns was described by Heftman. The RRt of some estrane, androstane, and pregnane derivatives was also reported. ... 

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