A4-Androstene-3,17-dione

Figure 4-12 The mechanism for the isomerization of A5 — A4-androstene-3,17-dione with optimized geometries for the seven key-structures.

Initially, Moffatt et al. performed optimization studies on the oxidation of testosterone (14) to A4-androstene-3,17-dione (15).14... 

Annelation of steroidal dienamines with substituted phenacyl bromides (7 examples) or with benzenediazonium salts (11 examples) has been shown to lead to the corresponding furano- and indolo-steroids.89 Thus the A3,5-dienamine derived from A4-androstene-3,17-dione reacted with p-bromophenacyl bromide to yield the A5-androstano[3,4-h]furan (199) in 26% yield, and reaction of the same A3,5-dienamine with benzenediazonium fluoroborate at -45 °C led to formation of the hydrazone (200) which underwent Fischer-indole cyclization on treatment with phosphorus oxychloride to produce the A4-androstano[6,7-6]indole (201). The A3,5-dienamine derived from 17/3-acetoxyandrost-4-en-3-one has been converted into the benz[4,5,6]-steroid (202 R1 = Me, R2 = H) by reaction with methyl vinyl ketone and into the analogous benzsteroid (202 R1 = H, R2 = Me) on treatment with crotonal-dehyde.90 A route to the condensed pyrroline ring system (203) has been devised... 

Several methods have been developed for establishing the MP2 limit for small molecules. We shall compare three of the most important methods, and a recently proposed combination of two of them that achieves a new level of efficiency in obtaining chemically accurate absolute MP2 energy limits. We conclude with a case study of the extension of these approaches to enzyme kinetics, namely the A5-ketosteroid isomerase-catalyzed conversion of A5-androstene-3,17-dione to the A4 isomer. 

Figure J. 10 A5-ketosteroid isomerase-catalyzed conversion of As-androstene-3,17-dione to the A4 isomer.

Application of CBS extrapolations to the A5-ketosteroid isomerase-catalyzed conversion of A5-androstene-3,17-dione to the A4 isomer (Fig. 4.10) provides a test case for extensions to enzyme kinetics. This task requires integration of CBS extrapolations into multilayer ONIOM calculations [56, 57] of the steroid and the active site combined with a polarizable continuum model (PCM) treatment of bulk dielectric effects [58-60], The goal is to reliably predict absolute rates of enzyme-catalyzed reactions within an order of magnitude, in order to verify or disprove a proposed mechanism. 

A -5-Androstadiene-3,17-dione, 461, 462 5 -Androstane-17/S-ol, 377 5a-Androstane-16-one, 243 5< -Androstane-17-one, 243 5a-Androstane-3-one-17fl-ol, 377 Androstanol-3j8, 363 Androstanone-3, 363 A -Androstene-3, 17-dione, 165 A5-Androstene-3/3-ol, 73 A4-Androstene-3,l 1,17-trione, 354 1 Androsterone, 286... 

This investigation was further extended to the synthesis of inhibitors of type 3 17 3-hydroxy-steroid dehydrogenase (17(3-HSD), a key steroidogenic enzyme transforming the inactive androgen 4-androstene-3,17-dione (A4-dione) into testosterone (Figure 11.54). This enzyme constitutes an... 

Degradation of the Side Chain of A4-Pregnene-ll, 17,20,21-tetrol-3-one (VIII) by Periodic Acid Oxidation.68 Small-Scale Oxidation. To a solution of 25 mg. of A4-pregHene-ll,17,20,21-tetrol-3-one in 1.5 cc. of methanol is added a solution of 40 mg. of periodic add in 0.3 cc. of water. After twenty hours the solution is diluted with water and freed from methanol in vacuum. The residue is extracted with ethyl acetate and ether. The extract is washed with water and sodium carbonate solution, and then dried over anhydrous sodium sulfate. The crystalline neutral product, obtained by evaporation of the solvent, is recrystallized from ether, then sublimed at 160° and 0.01 mm., and finally recrystallized from a mixture of ether and pentane. The yield of hygroscopic, fine needles of A4-androstene-ll-ol-3,17-dione (IX) melting at 189-191° (cor.) is 12 mg., or 60%. 

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