Pyridine Aldosterone

A photochemical partial synthesis of aldosterone (19) made the hormone available on an industrial scale for the first time (114). Corticosterone acetate (51 acetate) is treated with nitrosyl chloride in pyridine at 20°C to yield the 11-nitrite (115). Irradiation of (115) leads to rearrangement with formation of the C g-oxime (116). Removal of the oxime residue with nitrous acid furnishes aldosterone (19) in excellent yield. 

Aldosterone Aldosterone, llj3,21-dihydroxypregn-4-en-2,18,20-trione (27.2.4), is synthesized from 21-0-acetylcorticosterone, which when reacted with nitrosyl chloride in pyridine gives the nitrite 27.2.1. When photochemically irradiated, this compound is transformed to the oxime 27.2.2, which is hydrolyzed by nitrous acid and forms the semiacetal 27.2.3, which is an acetate of the desired aldosterone. Alkaline hydrolysis of the acetyl group of this compound leads to the desired aldosterone (27.2.4) [33]. 

Barton reaction In the Barton reaction " a methyl group in the 7 -position to an OH group is converted into an oxime group. For example, corticosterone acetate (2.45) on reaction with nitrosyl chloride (NOCl) in pyridine forms its 1 l -nitrite 2.46, which on photolysis in toluene gives aldosterone acetate oxime (2.47) in 21% yield. Treatment of 2.47 with nitrous acid (HNO2) gives aldosterone acetate (2.48) (Scheme 2.40). 

In addition, Al,0-bis-trimethylsilyltrifluoroacetamide has been used very effectively for the silylation of estradiol and catechol estrogens. Employing Al,0-bis-trimethylsilyltrifluoro-acetamide pyridine trimethylchlorosilane (5 5 1 v/v/v) at 40°C for 8-10 hr, tetrahydroaldosterone (ll(3,18-epoxy-3a, 16,21-trihydroxy-5 (3-pregnene-20-one) and aldosterone (11 3,21-dihydroxy3,20-dio-exopregn4-en-18-al)... 

---