A Dash of Proline Makes Things Sweet

摘要

Hexose carbohydrates come in many forms, including the common sugar glucose, and are integral to biological processes as diverse as cell signaling, inflammation, the immune response, and tumor cell metastasis (7). Each function is specific to a particular form of hexose, but studying how structure relates to function is limited by the difficulty of obtaining pure samples of the hexoses and their derivatives. The de novo construction of complex, differentiated carbohydrates by chemical synthesis is feasible but challenging owing to the structural and stereochemical complexity of these polyhydroxylated compounds. The ideal strategy for synthesizing the hexose carbohydrates would join three simple, alpha-oxygenated, two-carbon aldehydes by sequential aldol addition reactions with high enantio- and diastereoselectivity. On page 1752 of this issue, Northrup and MacMillan (2) describe remarkable, two-step, stereo-selective syntheses of several polyol-differ-entiated hexoses from achiral two-carbon building blocks. A dash of the amino acid L-proline (1) and classical organic chemical reactivity are the keys to this powerful new synthesis of these six-carbon sugars.