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C. Stanetty, I. Baxendale, M.D. Mihovilovic:
"Simple access to L-glycero-D-manno heptose at scale - a milestone towards more convenient syntheses of bacterial LPS-substructures";
Vortrag: 28th International Carbohydrate Symposium, New Orleans, Louisiana, USA; 17.07.2016 - 21.07.2016.

The seven-carbon sugar L-glycero-D-manno-heptose (LD-heptose, 1) is a major constituent of the inner core region of the lipopolysaccharide (LPS) of many Gram-negative bacteria. All established syntheses to this rare sugar require multiple steps and purifications, a drawback regularly addressed by installing the desired protecting group pattern alongside the chain elongation. We are convinced that a simpler (commercial) access to LD-heptose will greatly encourage more variable strategies towards the building blocks required for the assembly of oligoheptoside target structures. Such strategies greatly facilitate the late-stage optimization of the glycosyl donor and acceptor compared to an early introduction of the protecting group pattern.

In this light, we have recently accomplished a short and scalable process towards LD-heptose 1 and its crystalline, bench-stable α-pyranose peracetate 2. With an indium mediated acyloxyallylation of unprotected L-lyxose as the key transformation and only two recrystallizations pure 2 was obtained at >100mmol scale in single batch operations.[1] Next, we set out to establish a reliable methodology for the fast and variable preparation of heptose building blocks starting from 2. The presented approach is based on the exocyclic TIPDS-protection and its partial deprotection[2] (as in 4 to 5) and further utilizes a fine-tuned orthoester-methodology for the differentiation of the manno-configured endocyclic triol (3 to 4). It was applied to O- and S-glycosides of LD-manno and DD-manno configuration (as in the biochemical precursor of 1) and allows a variety of glycosylation building blocks to be prepared within a few days´ work.
[1] Stanetty, C.; Baxendale, I. R.; Eur. J. Org. Chem. 2015, 2015, 2718-2726.
[2] Stanetty, C.; Walter, M.; Kosma, P.; J. Org. Chem. 2014, 79, 582-598