Studies of the synthesis of sugar phosphonates related to 3-deoxy-D-manno-2-octulosonic acid (Kdo).
In attempting to synthesize the analogue of beta-Kdo (2R)-2-carboxy-6-(1',2'-dihydroxyethyl)-4,5-dihydroxy-D-manno-1,2 lambda 5-oxaphosphorinan-2-one (6) as an inhibitor of the enzyme CMP-Kdo synthetase, which is involved in the biosynthesis of the lipopolysaccharide component of the outer membrane of Gram-negative bacteria, (2R)-6-(1',2'-dihydroxyethyl)-2-ethoxy-3,4,5-trihydroxy-4,5:1', 2'-di-O-isopropylidene-D-glycero-D-talo-1,2 lambda 5-oxaphosphorinan-2-one (8) was converted into (2S)-6-(1',2'-dihydroxyethyl)-4,5-dihydroxy-4,5:1',2'-di-O-isop rop ylidene-2-vinyl-D-manno-1,2 lambda 5-oxaphosphorinan-2-one (16), but alkene cleavage to give the target carboxyphosphonate failed. Reduction-oxidation-Arbuzov reaction on the intermediate (2R)-6-(1',2'-dihydroxyethyl)-2-ethoxy-4,5-dihydroxy-4,5:1', 2'-di-O-isopropylidene-D-manno-1,2 lambda 5-oxaphosphorinan-2-one (11) gave the 2S isomer of the protected target compound, but removal of the protecting groups gave the acyclic product dilithium (D-manno-2,3,4,5,6-pentahydroxyhexyl)phosphinatoformate (24). N.m.r. studies of the intermediates allowed assignment of stereochemistry at P for all compounds via 2JP,H coupling constants.
Molin
H
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Department of Antibacterial Chemotherapy, Astra Alab AB, Södertälje, Sweden.
Norèn
J O
JO
Claesson
A
A
D002236:Carbohydrate Conformation; D003198:Computer Simulation; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009904:Optical Rotation; D063065:Organophosphonates; D013400:Sugar Acids / Q000138:chemical synthesis*
D007202:Indicators and Reagents; D063065:Organophosphonates; D013400:Sugar Acids; C002532:2-keto-3-deoxyoctonate