Logo image
Synthesis of Bleomycin-Disaccharide and Alginate Oligosaccharides
Dissertation

Synthesis of Bleomycin-Disaccharide and Alginate Oligosaccharides

Fa-Chen Chi
Doctor of Philosophy (PHD), 國立清華大學, 化學系
2005

Abstract

博菜黴素 藻酸 異葡萄糖 寡醣 雙醣 醣鏈結反應 Bleomycin Alginate Gulospyranose Oligosaccharide disaccharide glycosylation
This thesis is concerned with the syntheses of bleomycin-disaccharide and alginate oligosaccharides that both contain the rare L-gulopyranosyl sugars as basic components. 1,6-Anhydro-□-L-idopyranose 60, obtained from diacetone □-D-glucose 54 in three steps in 51% overall yield, was converted to the 1,6-anhydro-□-L-gulopyranosyl sugar 75 (72%) via one-pot O2-triflation and O3,O4-dibenzoylation followed by nucleophilic substitution with NaNO2 at C2. Consecutive O2,O4-dibenzoylation and O3-carbonylation of commercially available 1,6-anhydro-□-D-mannopyranose 73 provided the ester 77 (48%), which underwent acetolysis, anomeric deacetylation, and imidation to yield the corresponding imidate 80 (61%) in three steps. Coupling of 80 with 75 in the presence of TMSOTf led to the disaccharide 81 (82%), which was subjected to acetolysis followed by nucleophilic displacement with ammonia to afford the bleomycin-disaccharide moiety 83 in 57% yield. For the synthesis of alginate oligosaccharides, a four-stepped conversion of vitamin C via hydrogenation, isopropylidenation, DIBAL reduction, and acidic hydrolysis gave 1,6-anhydro-□-L-gulopyranose 88 in 56% overall yield, which was transformed into the donor 108 (81%) and the acceptor 104 (61%) in four and five steps, respectively. TMSOTf-activated coupling of 108 and 104 furnished the □-linked disaccharide 109 (70%), which was opened under acetolysis conditions followed by anomeric deacetylation to yield the 1-alcohol 112 (79%). The elongation cycle was then repeated twice to assemble the tri- and tetrasaccharides 116 and 120 through a four-stepped protocol [imidation-glycosylation- acetolysis-anomeric deacetylation], respectively. Anomeric allylation of 112, 116, and 120, individually, led to the □-linked ethers 121-123, which underwent sequential deacetylation, TEMPO oxidation, and reduction to afford alginate oligosaccharides 130-132, respectively.

Metrics

1 Record Views

Details

Logo image