L-Glycero-D-manno-heptose

Scheme 1) whereas the reaction with the D-man/io-hexodialdo-l,5-pyranose derivative 3 produced, in low yield, the cyanohydrin 4 having an L-glycero-D-manno configuration and the stereoisomeric epimer at C-5, rather than at C-6 [14J. With an atm toward the synthesis of d- and L-glycero-D-manno-heptoses, the reaction of 3 with other reagents (2-inethyl-furan, alkyl magnesium chlorides) was also explored, without any substantial improvement of either stereoselectivity or yield. 

M. Dasser, F. Chretien, and Y. Chapleur, A facile and stereospecific synthesis of L-glycero-D-manno-heptose and some derivatives, J. Chem. Soc. Perkin Trans. 7 3091 (1990). 

Biosynthesis of the most common constituent of the bacterial-lipopolysac-charide core, L-glycero-D-manno-heptose, was shown239,240 to occur through enzymic epimerization at C-6 of the heptosyl group in 9. Genetic evidence241,242 supports this pathway of biosynthesis. 

FIGURE 14.3 Structure of LPS with the core structure from Escherichia coli and the Salmonella species. Gal, galactose Glc, glucose Hep, L-glycero-D-manno-heptose O-PS, O-antigen polysaccharide. 

Despite the fact that many heptoses are by far less prominent in Nature than hexoses these monosaccharides are found both as metabolic intermediates, and as structural carbohydrates of bacterial cell walls.D-Sedoheptulose 7-phosphate is an important intermediate of the pentose cycle, and D-sedoheptulose 1,7-bisphosphate is present in plants as an intermediate of the dark phase of photosynthetic reactions. L-Glycero-D-manno-heptose was isolated from the oligosaccharides obtained by partial acid hydrolysis of the lipopolysaccharide from Escherichia coli K-12 strain W3100 [153] and Haemophilus influenzae [154]. Both L-glycero-D-wtanno-heptose and D-glycero-D-ma o-heptose were isolated from the lipopolysaccharide of Vibrio parahaemolyticus [155]. 

The structure of the core ohgosaccharides of Campylobacter jejuni 02 LPS was found to contain 3-deoxy-D-m nno-octulosonic acid (Kdo), L-glycero-D-manno-heptose (LD-Hep), D-Gal, D-Glc and phosphoethanolamine based on H, and P NMR. Molecular mimicry in C. jejuni LPS has been implicated in the pathogenesis of Guillain-Barre syndrome by inducing antibodies to human gangliosides. 

The LPS (endotoxin), which is a characteristic component of the outer membrane of Gram-negative bacteria, contains in the inner core (Scheme 3) two or three units of aheptose, generally L-glycero-D-manno-heptose (46). 

Some recent reports on the presence of L-glycero-D-manno-heptose (46) include the LPS of Pseudomonas syringae pv. atrofaciens IMV 948240 and the LPS of nontypeable Haemophilus influenzae strain 486.241 The LPS of Helicobacter pylori contains, in the inner core, both L-g/ycero-D-manno-heptose (LD-Hep) and D-glycero-D-manno-heptose (DD-Hep, 45), 242... 

Occurrence and preparation. L-glycero-D-gluco-Ueptose (52) is the major heptose present in the LPS, O-antigen polysaccharide, and core polysaccharide of Vibrio cholera Ogawa G-2102, together with small proportions of L-glycero-D-manno-heptose. The heptose was shown to be identical to an authentic sample (synthesized via condensation of L-galactose with nitromethane) and was isolated in pure state.257... 

L-glycero-D-manno-heptose represented in Scheme 2.1 is a major bacterial carbohydrate this carbohydrate and its D-glycero isomer are very often coined L,D-heptose (L,D-hep) and D,D-heptose (D,D-hep), respectively. 

Chapleur et al. [24] described a concise synthesis of i-glycero-D-tnanno-heptose from readily available aldehyde 23 previously prepared from alcohol 22 (Scheme 2.7). The condensation of aldehyde 23 with commercial vinylmagnesium bromide afforded a single alcohol 40 in 83% yield (Scheme 2.10). The benzylation of allylic alcohol 40 followed by oxidative cleavage of the double bond and reductive workup gave alcohol 41 which was further elaborated into L-glycero-D-manno-heptose 11 in 38% overall yield, after deprotections. 

Scheme 2.10 Stereoselective synthesis of L-glycero-D-manno-heptose 11.

---