Chain Extension of Carbohydrates VI. Synthesis of the Two C-6 Epimers of the 6-Acetylamino-4,6-dideoxyheptopyranosiduronic Acid Present in Amipurimycin by Means of Stereocontrolled Ethynylation of Methyl 2,3-Di-<i>O</i>-benzyl-4-deoxy-<i>α</i>-<scp>d</scp>-<i>xylo</i>-hexodialdo-1,5-pyranoside

Abstract

Abstract The two C-6 epimers of 6-acetylamino-4,6-dideoxy-heptopyranosiduronic acid present in amipurimycin were prepared by selective reactions from methyl 2,3-di-O-benzyl-4,6,7,8-tetradeoxy-α-l-ido-7-ynopyranoside (4) in which the ethynyl group was employed as a precursor of the carboxylic acid function. The masked amino group was introduced at C-6 by reaction of 4 with zinc azide in the presence of triphenylphosphine and diisopropyl azodicarboxylate. The resulting methyl 6-azido-2,3-di-O-benzyl-4,6,7,8-tetradeoxy-α-d-gluco-oct-7-ynopyranoside (5) was transformed into benzyl[6-(acetylamino)-2,3-di-O-benzyl-4,6-dideoxy-α-d-gluco-heptopyranosid]uronate (7) by two different sequences of reactions: (1) oxidative cleavage of the triple bond, benzylation, reduction of the azido group, N-acetylation or (2) reduction of the azido group, N-acetylation, oxidative cleavage of the triple bond and treatment with phenyldiazomethane. The second sequence of reactions was found to be more efficient (33% overall yield versus 13%). The configuration at C-6 was unambiguously confirmed by X-ray diffraction with a single crystal of 7. Final hydrogenolysis of benzyl groups afforded methyl 6-(acetylamino)-4,6-dideoxy-α-d-gluco-heptopyranosiduronic acid (9). A Mitsunobu reaction on acetylenic alcohol 4 followed by saponification afforded the C-6 epimer 11. The same sequences of reactions was applied to 11 and methyl 6-(acetylamino)-4,6-dideoxy-α-l-ido-heptopyranosiduronic acid (16) was obtained.