IONOPHORE ANTIBIOTIC X-14547A ENANTIOSELECTIVE SYNTHESIS OF THE TETRAHYDROPYRAN UNIT; STUDIES DIRECTED TOWARDS THE TOTAL SYNTHESIS OF AMPHOTERICIN B. SYNTHESES OF O-GLYCOSIDES AND GLYCOSYL FLUORIDES.

摘要

Enantioselective total synthesis of the tetranydropyran building block I for the total synthesis of ionophore antibiotic X-14547A is described.;The synthesis of the (C(,21)-C(,37)) fragment of the polyene macrolide antibiotic Amphotericin B has been accomplished in an enantio- selective manner, beginning with the (S,S)-1,4-bis(benzyloxy)2,3-epoxybutane. The key step involves an aldol condensation between ((alpha)S,4S)-(alpha),2,2-trimethyl-1,3-dioxolane-4-acetaldehyde and (4R,5S)-3-propionyl-4-methyl-5-phenyloxazolidone.;Phenyl thioglycosides can serve as stable intermediates for further elaboration in carbohydrate related areas. Specifically treatment of the readily available phenyl thioglycosides with N-bromosuccinimide in the presence of various hydroxy components under anhydrous conditions at 25(DEGREES)C yielded a series of O-glycosides in a few minutes. Phenyl thioglycosides were also converted to glycosyl fluorides.;The synthesis of the tetrahydropyran unit I in its optically active form involves convergence from the (R,R)-1,4-bis(benzyloxy)-2,3-epoxybutane to intermediates (2R)-2-(4S)-2,2-dimethyl-1,3-dioxolan-4-yl propyl triphenylphosphonium iodide and (2S,3S)-4-(benzyloxy)-2-(tert-butyldiphenylsiloxy)-3-methylbutyraldehyde followed by coupling and elaboration to the final target via an epoxide opening-ring closure reaction accompanied by one inversion, a sequence that sets all four asymmetric centers, in their correct stereochemistry.