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Synthesis of gluco ‐Configured Tetrahydroimidazopyridine‐2phosphonate‐Derived Lipids, Potential Glucosyl Transferase Inhibitors
Author(s) -
Billault Isabelle,
Vasella Andrea
Publication year - 1999
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19990804)82:8<1137::aid-hlca1137>3.0.co;2-n
Subject(s) - chemistry , salt (chemistry) , alcohol , acetylation , transferase , dolichol , silylation , hydrolysis , pyrrole , methylation , imidazole , organic chemistry , stereochemistry , medicinal chemistry , enzyme , catalysis , biochemistry , biosynthesis , gene
The analogues 1 – 3 of dolichol monophosphatidyl β ‐ D ‐glucose have been prepared as potential inhibitors of the glucosyl transferase Alg10p. Pd(PPh 3 ) 4 ‐catalysed phosphonylation of the iodoimidazole 4 with diethyl, dimethyl, and diphenyl phosphite led to the corresponding phosphonic acid diesters, which were transformed into deprotected and silyl‐protected diesters, deprotected monoesters, and protected and unprotected phosphonic acids ( Scheme ). A N ‐methyl imidazolium salt was obtained as a by‐product of the dimethyl‐phosphonylation of the iodoimidazole, and prepared in high yields by methylation of the imidazole 8 with MeI; the corresponding deprotected salt 11 inhibits sweet almond β ‐glucosidases ( IC 50 =308 μ M ). Trichloroacetonitrile‐promoted monoesterification of the acetylated mono‐triethylammonium salt 19 with oleyl alcohol, phytanol, and dolichol‐19, followed by deacetylation, gave the desired glycophospholipids.