No abstract

A new hydrolase for conjugated bile acids, tentatively named chenodeoxycholyltaurine hydrolase, was purified to homogeneity from Bacteroides vulgatus. This enzyme hydrolyzed taurine-conjugated bile acids but showed no activity toward glycine conjugates. Among the taurine conjugates, taurochenodeoxycholic acid was most effectively hydrolyzed, tauro-beta-muricholic and ursodeoxycholic acids were moderately well hydrolyzed, and cholic and 7 beta-cholic acids were hardly hydrolyzed, suggesting that this enzyme has a specificity for not only the amino acid moiety but also the steroidal moiety. The molecular weight of the enzyme was estimated to be approximately 140,000 by Sephacryl S-300 gel filtration and the subunit molecular weight of the enzyme was 36,000 by SDS-polyacrylamide gel electrophoresis. The optimum pH was in the range of 5.6 to 6.4. The NH2-terminal amino acid sequence of the enzyme was Met-Glu-Arg-Thr-Ile-Thr-Ile-Gln-Gln-Ile-Lys-Asp-Ala-Ala-Gln. The enzyme was activated by dithiothreitol, but inhibited by sulfhydryl inhibitors, p-hydroxymercuribenzoate, N-ethylmaleimide, and dithiodipyridine.

Myriceric acid A (1) is an oleanane triterpene that is a potent and specific endothelin A receptor antagonist. A practical procedure for large-scale synthesis of myriceric acid A (1) has been developed starting from oleanolic acid 4. The conversion of oleanolic acid 4 to the key intermediate myricerone 3 was achieved in an efficient manner employing a photochemical reaction (the Barton reaction) of nitrite 7. Our synthetic procedure alleviated several difficulties of the original Barton's procedure with regard to yields and large-scale operation. Myricerone 3 afforded Horner−Wadsworth−Emmons (HWE) type phosphonate 2 which has proved to be a versatile precursor of 1. The preparation of phosphonate 2 on a scale of several hundred grams is described. The synthesis was completed by condensation of 2 with 3,4-bis[(diphenylmethyl)oxy]benzaldehyde (21), giving α,β-unsaturated ester 22, which was deprotected to afford 1. The whole synthetic sequence is efficient (14 steps, 31% yield) and requires no chromatographic purification except to obtain the final product 1.

No abstract

No abstract