Pregnane derivatives compounds

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... 

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. 

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. ... 

The second method uses the pregnane derivative XI as a starting material. This compound, on hydroxylation with osmium tetroxide, afforded the diol Xlla. This diol was then converted to the androstane analogue X. The same approach was independently published also by Hondo and Mori (3). As a by-product of hydroxylation of olefin XI with osmium tetroxide, we obtained 2B,3B-diol XIV and, from this, the lactone XV. However, when we treated XII (a corresponding diacetate, respectively) with trifluoroperacetic acid we found that oxidation of the side chain surprisingly proceeded much faster than oxidation of the B ring. Thus we obtained not only compound X but also an intermediate, compound XHIb, and on hydrolysis compound Xllla, that is the androstane analogue of castasterone ... 

The second structural class of steroidal progestins consists of pregnane derivatives like medroxyprogesterone acetate (MPA) (9), megestrol acetate (10) or cyproterone acetate (11). The introduction of a 17a-acetoxy group and different substituents in the 6-position of the parent molecule progesterone leads to an increase in metabolic stability and to orally active compounds. Cyproterone acetate was the first progestin... 

Solasodine (1) and related Solanum alkaloids are useful starting materials for the commercial preparation of steroid hormones." In particular the pregnane derivative (6) was prepared from solasodine in 65% overall yield via the intermediates (2), (3), and (4). The oxidative cleavage of the 20(22) double bond of pseudosolasodine diacetate (3), which is the least efficient step in this synthesis, has been investigated in more detail With sodium dichromate in acetic acid compound (3) gave the hydroxyester (5) and the hydroxylactone (7), in addition to the ester (4). Results of a kinetic study of this reaction were interpreted in terms of formation of hydroxyester (5) via allylic oxidation of pseudosolasodine diacetate prior to cleavage of the 20(22) double bond. ... 

Androstene and pregnane derivatives were reacted with syngas and some amino alcohols ([RhCl(NBD)]2 (NBD = norbornadiene), phosphine, CO/H2 = l l, 80 bar benzene) to afford the corresponding hydroxyalkyl/aryl compounds in yields of 70-93% as shown below (Figure 5.21) [89]. Monodentate phosphines, PBuj and PPhj, induced the highest yields of amines, whereas with DlOP as a ligand the multistep sequence stopped at the stage of the imine. Under all conditions, the diastereomeric a/p-ratio was close to 1. 

It now appears that the de novo formation of pregnane derivatives in nature proceeds almost certainly by the side-chain cleavage of preformed sterols rather than by direct formation from acetate. The existence of an alternate pathway for the formation of pregnane compounds from acetate along routes not involving the prior transformation to squalene and its cyclization has not been demonstrated. No-... 

The signal assignments of the parent compounds 5 a- and 5 /i-androstane, 5 a- and 5 /i-pregnane and estrane [564] were performed by comparing the spectra with closely related derivatives, using substituent effects, off-resonance decoupled spectra and specifically deuterium-labeled analogues [564], The influence of different structural environments on the 13C chemical shift of the carbonyl carbon in keto steroids is illustrated by the values given in Table 5.10 [566]. The carbonyl carbon atom frequency in cyclopen-tanone moieties is shifted about 5 ppm downfield relative to that in cyclohexanone... 

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