Linear total synthetic routes to β-D-C-(1,6)-linked oligoglucoses and oligogalactoses up to pentaoses by iterative Wittig olefination assembly

Article abstract of DOI:10.1021/jo011142u

Two complementary routes, A and B, have been followed for the stepwise iterative assembly of β-D-(1,6)-glucopyranose and galactopyranose residues through methylene bridges. In route A the building block was constituted by 2,3,4-tri-O-benzyl-6-O-tert-butyldiphenylsilyl (O-TBDPS) β-linked galactosylmethylenephosphorane, while in route B the building block was a β-linked formyl C-glycopyranoside with a similar orthogonal protection of hydroxy groups. In route A each cycle consisted of the reaction of the phosphorane building block with a sugar residue bearing a formyl group at the C-5 carbon atom (coupling) and transformation of the O-TBDPS-protected primary alcohol into the formyl group (arming). Accordingly, route A is defined as the aldehyde route. On the other hand, each cycle in route B involved the coupling of the sugar aldehyde building block with a substrate bearing a phosphorus ylide at C-6 and introduction of the phosphonium group in the arming step as a precursor of the ylide functionality. Accordingly, route B is defined as the ylide route. The efficiency of route A proved to be seriously hampered by the 1,2-elimination of BnOH under the basic reaction conditions of the Wittig olefination, giving rise to the formation of substantial amounts of enopyranose. On the other hand, the ylide route B proved to be more efficient since very good yields (70-93%) of the isolated Wittig products were obtained throughout four consecutive cycles. Individual olefins and polyolefins obtained by routes A and B using gluco and galacto substrates were reduced and debenzylated in one pot by H₂/Pd(OH)₂ to give the corresponding β-D-C-(1,6)-linked oligosaccharides up to the pentaose stage. The latter compounds were fully characterized by high-field NMR spectroscopy (500 MHz).