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Galactosylated 5‐Hydroxylysine Mimetics for Glycopeptide Synthesis
Author(s) -
Marin Julien,
Violette Aude,
Briand JeanPaul,
Guichard Gilles
Publication year - 2004
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/ejoc.200400119
Subject(s) - chemistry , hydroxylysine , glycopeptide , enantiopure drug , stereochemistry , bromide , sodium borohydride , glycosylation , yield (engineering) , diol , enantioselective synthesis , amino acid , combinatorial chemistry , lysine , biochemistry , organic chemistry , catalysis , materials science , metallurgy , antibiotics
The design and synthesis of four galactosylated 5‐hydroxylysine mimetic building blocks ( 2 − 5 ), conveniently protected for solid‐phase glycopeptide synthesis, is described. Our approach features: i ) a short and divergent route to the corresponding protected amino acid aglycons 6 − 9 that involves selective ring‐opening of enantiopure 5‐hydroxylated 6‐oxo‐1,2‐piperidinedicarboxylate 10 and 11 with sodium borohydride in ethanol with formation of the corresponding 1,2‐diol; ii ) a common δ‐lactam precursor 12 , readily accessible from Boc‐Asp‐O t Bu (3 steps, 74% yield), that can be hydroxylated with a high level of asymmetric induction; iii ) the use of tetra‐pivaloylated galactosyl bromide as galactosyl donor to avoid or limit orthoester formation. The four galactosylated hydroxylysine analogues 2 − 5 are suitable building blocks for incorporation into immunodominant peptides derived from type II collagen (CII) and for future investigations aimed at determining the fine specificity of arthritogenic T‐cells in collagen‐induced arthritis (CIA), a mouse model for rheumatoid arthritis (RA). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)