1. Two-step synthesis of carbohydrates by selective aldol reactions
Alan B Northrup, David W C MacMillan Science. 2004 Sep 17;305(5691):1752-5. doi: 10.1126/science.1101710. Epub 2004 Aug 12.
Studies of carbohydrates have been hampered by the lack of chemical strategies for the expeditious construction and coupling of differentially protected monosaccharides. Here, a synthetic route based on aldol coupling of three aldehydes is presented for the de novo production of polyol differentiated hexoses in only two chemical steps. The dimerization of alpha-oxyaldehydes, catalyzed by l-proline, is then followed by a tandem Mukaiyama aldol addition-cyclization step catalyzed by a Lewis acid. Differentially protected glucose, allose, and mannose stereoisomers can each be selected, in high yield and stereochemical purity, simply by changing the solvent and Lewis acid used. The reaction sequence also efficiently produces (13)C-labeled analogs, as well as structural variants such as 2-amino- and 2-thio-substituted derivatives.
2. Highly stereoselective de novo synthesis of L-hexoses
Annalisa Guaragna, Daniele D'Alonzo, Concetta Paolella, Carmela Napolitano, Giovanni Palumbo J Org Chem. 2010 Jun 4;75(11):3558-68. doi: 10.1021/jo100077k.
An efficient and general de novo synthetic route to enantiomerically pure L-hexoses has been accomplished starting from the heterocyclic homologating agent 5,6-dihydro-1,4-dithiin-2-yl[(4-methoxybenzyl)oxy]methane and methyl alpha,beta-isopropylidene-L-glycerate. The sugar scaffold was constructed by an acid-catalyzed domino reaction, which enabled selective preparation of either methyl 2,3-dideoxy-alpha-L-threo-hex-2-enopyranosides or 1,6-anhydro-2,3-dideoxy-beta-L-threo-hex-2-enopyranose as key intermediates. The subsequent double bond functionalization by syn or anti dihydroxylation reactions allowed introduction of the remaining stereogenic centers, leading to desired orthogonally protected L-hexopyranosides with a high degree of diastereoselectivity and with very good overall yields. These and previous results (based on the use of the corresponding L-erythro epimers) contribute to make our approach general and place it among the few methods able to synthesize the whole series of the rare L-hexoses.
