Remarkable beta-selectivity in the synthesis of beta-1-C-arylglucosides: stereoselective reduction of acetyl-protected methyl 1-C-arylglucosides without acetoxy-group participation.
An efficient and practical process to generate beta-C-arylglucoside derivatives was achieved. The process described involves Lewis acid mediated ionic reduction of a peracetylated 1-C-aryl methyl glucoside derived from the addition of an aryl-Li to selectively protected delta-D-gluconolactone. The reduction of the 2-acetoxy-1-C-oxacarbenium ion intermediates proceeds with a high degree of selectivity to give beta-C-arylglucosides without 2-acetoxy group participation. Furthermore, during the reduction process we also identified an unprecedented critical role of water. By changing from the usual benzyl ether protecting groups because of cost and chemical compatibility concerns, the new process is made additionally efficient and highly selective.
Deshpande
Prashant P
PP
Process Research and Development, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, USA. prashant.deshpande@bms.com
Ellsworth
Bruce A
BA
Buono
Frederic G
FG
Pullockaran
Annie
A
Singh
Janak
J
Kissick
Thomas P
TP
Huang
Ming-H
MH
Lobinger
Hildegard
H
Denzel
Theodor
T
Mueller
Richard H
RH
D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013997:Time Factors
D005960:Glucosides