11 -Deoxycorticosterone, from progesterone 18-hydroxylation

Hydroxylation has been studied only in terms of aldosterone biosynthesis. A detailed investigation of precursors of this mineralocorticoid has been conducted and is described in full by Ayres et al. (1960). Corticosterone is transformed somewhat more rapidly than deoxycorticosterone or progesterone (Fig. 18). 18-Hydroxydeoxycorticosterone has been isolated from incubations of rat adrenal sections in the presence of TPNH and oxygen (Peron, 1961). Its further conversion (11/3-hydroxylation) to aldosterone, however, has not been reported. 

Progesterone is synthesized from either cholesterol or alkylated plant sterols by a pathway similar to that in animals. Hydroxylation at C-20 and C-22 is a prerequisite for removal of the C-6 residue of the side chain (A, B, C, Fig. 16). The product pregnenolone is then reduced to progesterone (D, Fig. 16). Traces of oestrone, testosterone, deoxycorticosterone and closely related compounds have been found in plants but nothing is known of their biosynthesis. 

HvdroxYlation. The first reports of 15/3-hydroxylation were from Fried and associ ites i AiPhycomycesblakesleeanus on progesterone (F-285 - F-288) and from Meystre, Vischer, and Wettstein with Lenzites abietina on deoxycorticosterone (M-585, W-1087). The 15/3-hydroxylation of Compound S goes especially well with Bacillus megaterium (H-382). 

P450 21A2 is the enzyme involved in the 21-hy-droxylation of progesterone and 17-hydroxy-progesterone, yielding deoxycorticosterone and 11-deoxycortisol from the two substrates, respectively (Fig. 9.12). The 21-hydroxylation reaction is an important step in the synthesis of glucocorticoids and mineralocorticoids, and de-... 

Pathways not involving 17 a-hydroxylation are not altered, and there is no decrease in deoxycorticosterone, which derives from the 21-hydroxylation of progesterone, and corticosterone, which is formed by the 11 j8-hydroxylation of deoxycorticosterone. 

---