Two-Step Synthesis of Carbohydrates by Selective Aldol Reactions
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 α-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.
Additional Information© 2004 American Association for the Advancement of Science. 21 June 2004; accepted 22 July 2004; published online 12 August 2004. Financial support was provided by the NIH National Institute of General Medical Sciences (R01 GM66142-01) and gifts from Bristol-Myers Squibb, Johnson and Johnson, Eli Lilly, and Merck Research Laboratories. D.W.C.M. is grateful for support from the Camille and Henry Dreyfuss Foundation, the Sloan Foundation, and Research Corporation under the Cottrell Scholarship and Research Innovation programs. A.B.N. is grateful for an NSF predoctoral fellowship.
Supplemental Material - Northrup_SOM.pdf