CHAIN EXTENSION OF CARBOHYDRATES .6. SYNTHESIS OF THE 2 C-6 EPIMERS OF THE 6-ACETYLAMINO-4,6-DIDEOXYHEPTOPYRANOSIDURONIC ACID PRESENT IN AMIPURIMYCIN BY MEANS OF STEREOCONTROLLED ETHYNYLATION OF METHYL ZYL-4-DEOXY-ALPHA-D-XYLO-HEXODIALDO-1,5-PYRANOSIDE

The two C-6 epimers of 6-acetylamino-4,6-dideoxy-heptopyranosiduronic acid present in amipurimycin were prepared by selective reactions from methyl zyl-4,6,7,8-tetradeoxy-alpha-L-ido-7-ynopyranoside (4) in whic h 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 diisoprop yl azodicarboxylate. The resulting methyl 6,7,8-tetradeoxy-alpha-D-glu co-oct-7-ynopyranoside (5) was transformed into l-4,6-dideoxy-alpha-D- gluco-heptopyranosid]uronate (7) by two different sequences of reactio ns: (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 wi th phenyldiazomethane. The second sequence of reactions was found to b e more efficient (33% overall yield versus 13%). The configuration at C-6 was unambiguously confirmed by X-ray diffraction with a single cry stal of 7. Final hydrogenolysis of benzyl groups afforded methyl )-4,6 -dideoxy-alpha(-)D-gluco-heptopyranosiduronic acid (9). A Mitsunobu re action on acetylenic alcohol 4 followed by saponification afforded the C-6 epimer 11. The same sequences of reactions was applied to 11 and methyl mino)-4,6-dideoxy-alpha-L-ido-heptopyranosiduronic acid (16) wa s obtained.