Stereospecific Synthesis of the Saccharosamine-Rhamnose-Fucose Fragment Present in Saccharomicin B

Abstract

A synthetic route has been developed for constructing the d-saccharosamine-l-rhamnose-d-fucose (Sac-Rha-Fuc) trisaccharide fragment present in the antibacterial natural product saccharomicin B. The Sac monosaccharide was synthesized through a modified nine step procedure starting from d-rhamnal in 23% overall yield. 1- O-TBS Sac donors were used to construct the β-linked Sac-Rha disaccharide. This disaccharide was coupled to a Fuc acceptor under BSP/TfO conditions to afford a trisaccharide properly functionalized for elaboration to saccharomicin B.

Glycosyl Sulfonates Beyond Triflates

“…Such information will be useful in further optimizing reactions with substrates that have proven to be challenging, such as the protected saccharosamine 35 which undergoes α‐selective reactions under our standard conditions for glycosylation (Scheme 8). [37] …”

Dissection of the Glycosylation in the Biosynthesis of the Heptadecaglycoside Antibiotic Saccharomicin A

“…SA-A and SA-B display potent activities against Gram-positive bacteria and are also active (albeit with decreased activities) against Gram-negative bacteria . Despite extensive efforts, − total synthesis of these two heptadecaglycosides has not been achieved thus far.…”

Synthesis of the Non-Reducing Hexasaccharide Fragment of Saccharomicin B

“…4 Very recently, our laboratory has reported efficient and stereoselective routes to the Fuc-8 to Dig-10 branching point and the Fuc-5 to Sac-7 fragment of saccharomicin B (Figure 1). 5 Herein, we report the first synthetic route to the nonreducing hexasaccharide fragment of saccharomicin B which corresponds to the Fuc- 12 to Eva-17 sector, which would be the largest fragment of the molecule so far synthesized.…”

“…6 Tetrasaccharide 3 could ultimately be traced back to three suitably functionalized monosaccharides: L -digitoxose 6, L -4- epi -vancosamine 8, and D - fucose 10. The L -4- epi -vancosamine 7 can be synthesized from vancomycin−HCl using our group’s modification 5a to the procedure described by Kahne and Walsh. 8 Similarly, L - digitoxose can be obtained from L -rhamnal as most recently described by our group 5a (for the preparation of the monosaccharides, see Supporting Information).…”

“…The L -4- epi -vancosamine 7 can be synthesized from vancomycin−HCl using our group’s modification 5a to the procedure described by Kahne and Walsh. 8 Similarly, L - digitoxose can be obtained from L -rhamnal as most recently described by our group 5a (for the preparation of the monosaccharides, see Supporting Information). Meanwhile, disaccharide 4 could be obtained through glycosylation between L -4- epi -vancosamines 8 and 9.…”