A strategy for the solution-phase parallel synthesis of N-(pyrrolidinylmethyl)hydroxamic acids.
Both five- and six-membered iminocyclitols have proven to be useful transition-state analogue inhibitors of glycosidases. They also mimic the transition-state sugar moiety of the nucleoside phosphate sugar in glycosyltransferase-catalyzed reactions. Described here is the development of a general strategy toward the parallel synthesis of a five-membered iminocyclitol linked to a hydroxamic acid group designed to mimic the transition state of GDP-fucose complexed with Mn(II) in fucosyltransferase reactions. The iminocyclitol 8 containing a protected hydroxylamine unit was prepared from D-mannitol. The hydroxamic acid moiety was introduced via the reaction of 8 with various acid chlorides. The strategy is generally applicable to the construction of libraries for identification of glycosyltransferase inhibitors.
Takayanagi
M
M
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Flessner
T
T
Wong
C H
CH
D005647:Fucosyltransferases / Q000737:chemistry / Q000378:metabolism; D006154:Guanosine Diphosphate Fucose / Q000737:chemistry / Q000378:metabolism; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D008345:Manganese / Q000737:chemistry / Q000378:metabolism; D008353:Mannitol; D008968:Molecular Conformation; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D012996:Solutions
D006877:Hydroxamic Acids; D007202:Indicators and Reagents; D011759:Pyrrolidines; D012996:Solutions; D006154:Guanosine Diphosphate Fucose; D008353:Mannitol; D008345:Manganese; D005647:Fucosyltransferases