STEREOSELECTIVE SYNTHESIS AND ABSOLUTE STEREOCHEMISTRY OF SINEFUNGIN

Sinefungin has been synthesized from D-ribose, L-ornithine, and adenine. L-Ornithine was converted to its δ-nitro analogue 10, which was coupled to the ribose derived aldehyde 11 by a potassium fluoride catalyzed nitro-aldol reaction. The resulting nitro alcohol 12 was further transformed by dehydration and reduction of the nitrovinyl intermediate to the oxime, which was oxidatively cleaved to ketone 16. The proper (S) stereochemistry at C-6 resulted from a stereoselective hydride reduction of this ketone to the epimeric alcohols in a 92/8 ratio and an Sn2 displacement of the corresponding O-tosylate by azide anion. The stereochemistry at C-6 was proved by correlation with the pyrrolidine obtained by cyclization of the tosylate to the α-[(4-methylphenyl)sulfonyl]amino group. The absolute stereochemistry of the pyrrolidine was determined by X-ray crystallographic analysis. Conversion of the azide 23 to sinefungin was accomplished by conversion of the ribose moiety to the corresponding β-acetate, adenosylation, reduction of the azide group to amino, and cleavage of the tert-butyl ester and N-tosyl protecting groups. The resulting synthetic sinefungin is identical with the natural material, thus providing a stereoselective synthesis and unequivocally establishing the absolute stereochemistry at C-6 as S. © 1990, American Chemical Society. All rights reserved.