THE ADRENAL HORMONES AND RELATED COMPOUNDS. II. SYNTHESIS OF 1-DEHYDRO ANALOGS¹

Shortening Synthetic Routes to Small Molecule Active Pharmaceutical Ingredients Employing Biocatalytic Methods

“…In the initial study, 11α-hydroxyprogesterone was formed in only 10% yield by R. arrhizus (later improved to 50%), while R. nigricans furnished up to 97% yield owing to an improved protocol ( R. nigricans was grown over 24 h in 240 L of medium, before addition of 120 g of progesterone followed by 30 h of reaction time) (Scheme A) . This biohydroxylation was eventually integrated into Upjohn’s five-step hydrocortisone production process. ,, A number of steroid hormone analogues were subsequently integrated into the main-line process demonstrating its broad versatility . The original chemical commercial production of cortisone was started from deoxycholic acid via 31 steps, which was plagued by low overall yields (0.16%).…”

Spectrophotometric Determination of Residual Δ4-3-Ketosteroids in Bulk Δ1,4-3-Ketosteroids. Differential Rates of Thiosemicarbazone Formation

“…The nitration procedure described w'as suggested by the qualitative method in the British User's Memorandum (5) and by the ASTM method (1). Materials most likely to cause erroneous results may be removed by extraction, and those that remain unextracted (carbon black, fillers, and other polymers) interfere slightly, if at all.…”

A New Approach to 16α-Hydroxycorticoids1

“…The ultraviolet and infrared absorption spectra of 3 indicated that the new hydroxyl group of 2 was at position 16. Unequivocal proof of structure was obtained by acetylation of the 16-hydroxyl group followed by oxidation with osmium tetroxide-lV-methylmorpholine oxide peroxide5 6to yield 11/5,16 ,17a,21-tetrahydroxy-1,4-pregnadiene-3,20-dione 16,21-diacetate (4).20 An authentic sample of 4 was prepared by osmium tetroxide hydroxylation of 11/3,21 -dihydroxy-1,4,16-pregnatriene-3,20-dione 21-acetate (5)6 followed by acetylation. The identity of the two samples established that selenium dioxide oxidation introduced a 16a-hydroxy group into ll/3,21-dihydroxy-l,4,17(20)cí's-pregnatrien-3-one 21-acetate (1).…”