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Approach Toward a Generic Treatment of Gram‐Negative Infections: Synthesis of Haptens for Catalytic Antibody Mediated Cleavage of the Interglycosidic Bond in Lipid A
Author(s) -
van den Berg Richard J. B. H. N.,
Noort Daan,
MilderEnacache Elena S.,
van der Marel Gijs A.,
van Boom Jacques H.,
Benschop Hendrik P.
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199910)1999:10<2593::aid-ejoc2593>3.0.co;2-c
Subject(s) - chemistry , hapten , moiety , lipid a , cleavage (geology) , lactam , stereochemistry , combinatorial chemistry , conjugate , catalysis , antibody , glucosamine , yield (engineering) , bovine serum albumin , bacteria , biochemistry , geotechnical engineering , metallurgy , engineering , immunology , biology , mathematical analysis , genetics , materials science , mathematics , fracture (geology)
In order to develop a generic treatment for infections with Gram‐negative bacteria, we developed a synthesis of 2‐acylamino‐deoxynojirimycin derivatives ( 17 , 18 , 19 and 20 ), which will be used as haptens for raising catalytic antibodies capable of hydrolyzing the interglycosidic bond in the lipid A moiety of endotoxins. A key intermediate in the preparation of compounds 17 , 18 , 19 and 20 is 3,4,6‐tri ‐O‐ benzyl‐2‐[(benzyloxycarbonyl)amino]‐2‐deoxy‐ D ‐glucono‐δ‐lactam ( 6 ), which was prepared from known 3,4,6‐tri ‐O‐ benzyl‐2‐[(benzyloxycarbonyl)amino]‐2‐deoxy‐ D ‐glucosamine ( 1 ) in four steps in 47% overall yield. Antibodies were generated against 2‐[(6‐aminohexanoyl)amino]‐2‐deoxy‐ D ‐glucono‐δ‐lactam ( 17 ) coupled to the carrier protein bovine serum albumin.