|XU, PENG - National Institutes Of Health (NIH)|
|STEVENS, EDWIN - Western Kentucky University|
|French, Alfred - Al|
|KOVAC, PAVOL - National Institutes Of Health (NIH)|
Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/5/2015
Publication Date: 2/22/2015
Citation: Xu, P., Stevens, E., French, A.D., Kovac, P. 2015. Synthesis and molecular structure of the 5-methoxycarbonylpentyl a-Glycoside of the upstream, terminal moiety of the O-specific polysaccharide of vibrio cholerae O1, serotype inaba. Molecules. 20:2892-2902.
Interpretive Summary: This effort concerns development of vaccines for cholera. The molecule in question is intended for use in studies of the molecular basis for the specific interactions of a particular strain of the bacterium that causes a major type of cholera and the development of a vaccine based on carbohydrates. Most of the report concerns the chemical procedure for making the molecule, as well as its characterization by several methods. The three-dimensional molecular structure was determined by X-ray crystallography. The carbohydrate portion of the molecule is similar to structures in the main molecules of cotton and starch, and the interactions of the remainder of the molecule are similar to various treatments given to cotton for waterproofing or other advanced treatments. Studying the details of these interactions advanced knowledge of how such molecules interact. The most interesting finding was that one of the oxygen atoms was interacting fairly strongly with two hydrogen atoms that are attached to carbon as well as with a hydrogen atom attached to oxygen, a normal hydrogen bond. It was a surprise to find that one oxygen atom is involved with three such bonds. This information is of importance to scientists studying cholera, as well as being of interest to scientists who study structure-function relationships in chemically modified carbohydrate-based materials such as cotton fabric.
Technical Abstract: Trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed reaction of methyl 6-hydroxyhexanoate with 3-O-benzyl-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-levulinoyl-'-D-mannopyranosyl trichloroacetimidate followed by two-step deprotection (hydrogenolysis over Pd/C catalyst and Zemplén deacylation, to simultaneously remove the acetyl and levulinoyl groups) gave 5-(methoxycarbonyl)pentyl 4-(3-deoxy-Lglycero-tertronamido)-4,6-dideoxy-'-D-mannopyranoside. The structure of the latter, which was obtained in the analytically pure crystalline state, followed from its NMR and high-resolution mass spectra, and was confirmed by X-ray crystallography.