Synthesis of C-glycosyl compounds. Part 1. Reaction of ethyl isocyanoacetate with 2,3:5,6-di-O-isopropylidene-D-mannono-1,4-lactone

Abstract

Formylaminomethylenation of 2,3:5,6-di-O-isopropylidene-D-mannono-1,4-lactone (1) with ethyl isocyanoacetate (2) gave, as the major product, (E)-ethyl 3,6-anhydro-2-deoxy-2-formylamino-4,5:7,8-di-O-isopropylidene-D-manno-oct-2-enonate (3)(58%), which on hydrogenation gave ethyl 3,6-anhydro-2-deoxy-2-formylamino-4,5:7,8-di-O-isopropylidene-D-erythro-L-gluco-octonate (17), in almost quantitative yield. Base-catalysed equilibration of the D-erythro-L-gluco-octonate (17) gave a mixture of the L-allo-, L-altro-, L-gluco-, and L-manno-epimers [(23), (22), (17), and (19), respectively]. The configurations at C-2 and C-3 of these epimers were established by chemical and physical methods.

The D-erythro-L-gluco-epimer (17) and the D-erythro-L-manno-epimer (19) were degraded to ethyl 3,6-anhydro-2-deoxy-2-formylamino-4,5-O-isopropylidene-D-glycero-L-gluco-heptonate (37) and its D-glycero-L-manno-epimer (39), respectively. Acidic hydrolysis of compounds (17), (19), (37), and (39) gave the free amino-acids, L-2-(β-D-mannofuranosyl)-glycine (41), the analogous D-amino-acid (42), L-2-(β-D-lyxofuranosyl)-glycine (43), and the analogous D-amino-acid (44), in moderate yields.

In the presence of base, alcohols and thiols readily attacked the double bond of the oct-2-enonate (3) to give, for example, ethyl (ethyl 2-deoxy-2-formylamino-4,5:7,8-di-O-isopropylidene-α-D-manno-D-glycero-oct-3-ulo-3,6-furanosid)onate and its D-manno-L-glycero-epimer [(9) and (10)].