Convergent and Stereoselective Synthesis of Iminosugar-Containing Galf and UDP-Galf Mimicks: Evaluation as Inhibitors of UDP-Gal Mutase
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- 作者：Virginie Liautard ; Valé ; rie Desvergnes ; Kenji Itoh ; Hung-wen Liu ; Olivier R. Martin
- 刊名：Journal of Organic Chemistry
- 出版年：2008
- 出版时间：April 18, 2008
- 年：2008
- 卷：73
- 期：8
- 页码：3103 - 3115
- 全文大小：300K
- 年卷期：v.73,no.8(April 18, 2008)
- ISSN：1520-6904
文摘
The synthesis of a UDP-Galf analog incorporating a 1,4-dideoxy-1,4-imino-D-galactitol skeleton 
fchars/alpha.gif" BORDER=0>-linkedto UMP by a 3C-tether and of a series of related pyrrolidine galactofuranose mimicks is reported. Thesecompounds were obtained by way of the highly stereoselective reaction of silylated nucleophiles with aN-Cbz glucofuranosylamine which afforded the corresponding open-chain product with a 1,2-synstereochemistry, as predicted from pionneering studies from Kobayashi. Cyclization of these intermediatesafforded fchars/alpha.gif" BORDER=0>-C-glycosides of imino-galactofuranose carrying various functional groups in the aglycone.Further elaboration of the fchars/alpha.gif" BORDER=0>-C-allyl substituted derivative by cross-metathesis with a uridin-5'-ylvinylphosphonate provided, after deprotection, the desired original UDP-Galf mimicks. Cleavage of thebenzyl ether protecting groups in the iminosugar component using BCl3 proved critical to the success ofthe synthetic plan. Several of the new 1,4-dideoxy-1,4-imino-D-galactitol derivatives were evaluated asinhibitors of UGM (UDP-galactopyranose mutase) from Escherichia coli; however, none of them exhibitedless than mM activities toward this enzyme which catalyzes a crucial step of the biosynthesis ofgalactofuranose-containing bacterial cell-surface glycans.
fchars/alpha.gif" BORDER=0>-linkedto UMP by a 3C-tether and of a series of related pyrrolidine galactofuranose mimicks is reported. Thesecompounds were obtained by way of the highly stereoselective reaction of silylated nucleophiles with aN-Cbz glucofuranosylamine which afforded the corresponding open-chain product with a 1,2-synstereochemistry, as predicted from pionneering studies from Kobayashi. Cyclization of these intermediatesafforded fchars/alpha.gif" BORDER=0>-C-glycosides of imino-galactofuranose carrying various functional groups in the aglycone.Further elaboration of the fchars/alpha.gif" BORDER=0>-C-allyl substituted derivative by cross-metathesis with a uridin-5'-ylvinylphosphonate provided, after deprotection, the desired original UDP-Galf mimicks. Cleavage of thebenzyl ether protecting groups in the iminosugar component using BCl3 proved critical to the success ofthe synthetic plan. Several of the new 1,4-dideoxy-1,4-imino-D-galactitol derivatives were evaluated asinhibitors of UGM (UDP-galactopyranose mutase) from Escherichia coli; however, none of them exhibitedless than mM activities toward this enzyme which catalyzes a crucial step of the biosynthesis ofgalactofuranose-containing bacterial cell-surface glycans.