A NEW TOTAL SYNTHESIS OF CHUANGXINMYCIN AND THE STUDY OF ITS STEREOISOMERS

A new total synthesis of the unique indole containing antibiotic, chuangxinmycin was described. This compound was assembled from indole by a scheme that combined the silylation with the trimethylsilyl group displacement directly to produce a 4-sulfur-substituted indole. Further transformations involving acetylation at the indole 3-position, with a spontaneous intramolecular condensation to 1-acetyl-3,4-dehydrochuang-xinmycin ethyl ester and a cis hydrogen addition reaction with concurrent hydrolysis of the ester group furnished racemic chuangxinmycin.Racemic chuangxinmycin (3S, 4R and 3R, 4S enantiomers) when treated with S(-)-α-phenylethyl amine in methanol, (S)-α-phenylethyl amine-(3S, 4R)-chuangxinmycin salt was separated as bar crystals on cooling. (S)-α-phenylethyl amine(3R, 4S)-chuangxinmycin salt isolated as prisms from the mother solution. Both of them were treated with acid to produce (-)-chuangxinmycin and (+)-chuangxinmycin, respectively.Treatment of both (-)-chuangxinmycin and (+)-chuangxinmycin with KOH in dioxane or DMF containing water, followed by separating and purifying, resulted in (+)-epichuangxinmycin and (-)-epichuangxinmycin whose configuration have been confirmed to be 3S, 4S and 3R, 4R by spectral data.Among these four stereoisomers, only that having the natural configuration is active against bacteria. Conversion of The other three into chuangxinmycin was effective by the following route. The stereoisomeric esters were dehydrogenated by DDQ to give the 3,4-dehydro product in high yields, which was in turn hydrogenated and resolved, thus completing the first cycle.