SUGAR AND AMINO ACID SYNTHESIS WITH SPECIFIC LABELING

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A new approach to the controlled chiral synthesis isotopically labeled sugars and amino acids is proposed, based on the efficient homologation of chiral boronic esters with lithiated dichloromethane to form Alpha-chloro boronic esters with very high diastereoselection at the Alpha-carbon. Preliminary work has shown that this homologation works in the presence of Alpha- and Beta-alkoxy groups, and it thus appears that the process can be repeated to introduce as many adjacent oxygen-substituted chiral centers as desired. Both enantiomers of the useful chiral directing groups, pinanediol and 2,3-butanediol, are available, giving the chemist independent absolute control of the configuration at each chiral center. Because of the extremely high stereoselectivity and the fact that all of the carbon is derived from dichloromethane, this process appears particularly promising as a route to regiospecifically and stereospecifically labeled sugars. The synthesis of several common hexoses and pentoses is proposed. Preparations of glyceraldehyde having both a 13C and a stereospecific 2H label at C-3 and also of 1-3H-4-14C-ribulose-5-phosphate are outlined. The method also appears highly promising for preparing amino acids with specifically placed chiral labels, and for chirally labeled methyl groups. The ultimate aim of the work is to provide a simple means of obtaining any desired sugar, amino acid, or related structure with any isotopic labels in any set of specific positions that the biochemist wants in order to answer questions about mechanisms of enzyme reactions and metabolic pathways, which will provide basic biochemical information relevant to a wide variety of health problems.