Shoichi Hirai

Synthetic studies on β-lactam antibiotics. VII. Mild removal of the benzyl ester protecting group with aluminum trichloride☆

The benzyl ester protecting group in β-lactam derivatives can be cleanly removed by treatment with aluminum trichloride under mild conditions, preferably in the presence of anisole, to give the corresponding free acids in high yields.

Phosphonic acids—IX : Steroidal 21a-phosphonate esters☆☆☆

Abstract Dialkyl esters of steroidal 21a-phosphonic acids, which may be regarded as phosphonate analogs of 21-phosphate esters with the oxygen link replaced by a methylene group, were synthesized by the reaction of a trialkyl phosphite with a quarternary salt of a Mannich base derivative of a 20-keto steroid. In this way, the 21-dialkoxyphosphinylmethyl group, (RO) 2 P(O)CH 2 —, was introduced into pregnenolone, 17α-hydroxypregnenolone and 17α-acetoxypregnenolene, and the products converted by oxidation to the corresponding progesterone derivatives. The same steroid phosphonates also were obtained by the reaction of alcoholic trialkyl phosphite with the 20-keto-Δ 21(21a) -steroid formed by thermal decomposition of the Mannich base salt. Monodealkylation of the 21a-dialkyl phosphonate esters to furnish the corresponding monobasic acids was effected smoothly by warming with alcoholic sodium propylmercaptide, except in the case of 17α-acetoxy-20-ketosteroids where this reagent caused a condensation between the acetoxy group and the side chain accompanied by d -homoannulation. Although the reaction of 21-iodoprogesterone with triethyl phosphite or sodium diethylphosphonate gave only progesterone, 21-tosyloxyprogesterone reacted with triethyl phosphite to yield 21-diethoxyphosphinylprogesterone.