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 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.
Department of Chemistry, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Alan B
AB
Northrup
David W C
DW
MacMillan
D000143:Acids; D000447:Aldehydes / Q000737:chemistry; D002247:Carbon Isotopes; D002384:Catalysis; D003500:Cyclization; D019281:Dimerization; D006601:Hexoses / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D008968:Molecular Conformation; D015394:Molecular Structure; D011392:Proline / Q000737:chemistry*; D012997:Solvents; D013237:Stereoisomerism
D000143:Acids; D000447:Aldehydes; D002247:Carbon Isotopes; D006601:Hexoses; D012997:Solvents; C116609:3-hydroxybutanal; D011392:Proline