Pregnenolone reaction sequences

Hydrolysis of the acetate (71) followed by Oppenauer oxidation gives B-norcholest-4-en-3-one in high yield. An analogous reaction sequence can be used to prepare B-norprogesterone and derivatives of B-nortestosterone from pregnenolone acetate and dehydroepiandrosterone acetate, respectively."" ... 

Ozonization of A -steroids usually gives complex mixtures (however, see ref. 48). Ozonolysis became a practical step in the general synthesis of B-norsteroids with the discovery that added methanol" (or formaldehyde ) improves yields significantly. Thus, Tanabe and Morisawa prepared 5/ -hydroxy-6/ -formyl-B-norsteroids (74) from cholesterol acetate, dehydroepiandrosterone acetate and pregnenolone acetate in overall yields of 64-74% by the reaction sequence represented below. 

A reaction sequence has been published for the transformation of pregnenolone acetate into 18-acetoxy-3/3 -hydroxy- 14a -carda-5,20(22)-dienolide... 

E. Quantitative Studies on the Consecutive Reaction Sequences between Cholesterol and Pregnenolone 316... 

The most commonly postulated mechanism for the desmolase reaction has been the suggestion of the enzymatic consecutive reaction sequence cholesterol 20a-hydroxycholesterol — (22R)-20a,22-dihydroxycholesterol pregnenolone (Shimizu et al., 1961, 1962 Constantopoulos and Tchen, 1961). This hypothetical scheme was actually advanced on the basis of three suppositions (1) cholesterol is cleaved between C-20 and C-22, as was discussed in a previous section, (2) 20a-hydroxycholesterol was formed from cholesterol-4- C by a cow adrenocortical homogenate in the presence of 20a-hy-droxycholesterol as a trapping agent (Solomon et al., 1956), and (3) both 20a-hydroxycholesterol and (22R)-20a,22-dihydroxycholesterol are much more efficiently transformed to pregnenolone than is cho-... 

CYP17A catalyzes both the 17a-hydroxylation of progesterone and subsequent cleavage of the C17-C20 bond to give androstenedione (Fig. 4.49). A similar transformation sequence accoimts for the conversion of pregnenolone to dehydroepiandrosterone. The favored mechanism for this reaction involves formation of the hydroperoxy hemiacetal with the ferric hydroper-oxy anion of the enzyme, followed by 0-0 bond homolysis, C-C bond homolysis, and finally recombination of the compormd II equivalent with... 

The P450 llAl reaction proceeds in a three-step sequence, with generation of 22R)-20a, 22-dihy-droxycholesterol as an intermediate (Fig. 9.22) [1935]. Oxidative cleavage of the diol to pregnenolone and 4-methylpentanal (isocaproic aldehyde) completes the overall reaction. The mechanism of the last step is not completely clear, but some proposals have been presented [1936-1938]. 

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