Reagent-Controlled Synthesis of the Branched Trisaccharide Fragment of the Antibiotic Saccharomicin B

Abstract

A concise synthesis of a branched trisaccharide, α-l-Dig-(1 → 3)-[α-l-Eva-(1 → 4)]-β-d-Fuc, corresponding to saccharomicin B, has been developed via reagent-controlled α-selective glycosylations. Starting from the d-fucose acceptor, l- epi-vancosamine was selectively installed using 2,3-bis(2,3,4-trimethoxyphenyl)cyclopropene-1-thione/oxalyl bromide mediated dehydrative glycosylation. Following deprotection, l-digitoxose was installed using the AgPF₆/TTBP thioether-activation method to produce the trisaccharide as a single α-anomer. This highly functionalized trisaccharide can potentially serve as both a donor and an acceptor for the total synthesis of the antibiotic saccharomicin B.

Figure 1

Structures of saccharomicin B, the target trisaccharide 1, and the key deoxy-sugar monosaccharide building blocks (2–5).

Scheme 1

Synthetic Pathway for the L-4-epi-Vancosamine Building Block

Scheme 2

Synthetic Pathway for L-Digitoxose Building Blocks

Scheme 3

Synthetic Pathway for the D-Fucose Building Blocks

Scheme 4

Dehydrative Glycosylation of Disaccharide Acceptor 20 with L-Digitoxose Hemiacetal Donor 4

Scheme 5

Synthesis of the Target Trisaccharide 1