TY - JOUR
T1 - Two-step synthesis of carbohydrates by selective aldol reactions
AU - Northrup, Alan B.
AU - MacMillan, David W.C.
PY - 2004/9/17
Y1 - 2004/9/17
N2 - 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 13C-labeled analogs, as well as structural variants such as 2-amino- and 2-thio-substituted derivatives.
AB - 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 13C-labeled analogs, as well as structural variants such as 2-amino- and 2-thio-substituted derivatives.
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U2 - 10.1126/science.1101710
DO - 10.1126/science.1101710
M3 - Article
C2 - 15308765
AN - SCOPUS:4544236616
SN - 0036-8075
VL - 305
SP - 1752
EP - 1755
JO - Science
JF - Science
IS - 5691
ER -