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Synthesis and Evaluation of S ‐ and C(1) ‐Substituted Analogues of Lincomycin
Author(s) -
Collin MariePierre,
Hobbie Sven N.,
Böttger Erik C.,
Vasella Andrea
Publication year - 2009
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/hlca.200800343
Subject(s) - lincomycin , chemistry , alkylation , alkyl , glycosylation , aryl , thiol , stereochemistry , antibiotics , organic chemistry , catalysis , biochemistry
New thioglycosides and C(1) ‐alkylated thioglycosides ( S ‐ulosides) of lincomycin were synthesized, and their antibiotic activities were determined. The S ‐aryl and S ‐arylalkyl analogues 11a – 11i were obtained by S ‐glycosylation of the sulfoxides 7 with arenethiols, or by S ‐alkylation of the thiol 14 with alkyl bromides. Lincomycin derivatives 27, 32a, 32b, 38a, 38b, 44 , and 47 were prepared via Henry reaction or Michael addition of the lincosamine‐derived 1‐deoxy‐1‐nitropyranoses 22 . The S ‐alkyl derivatives showed a similar activity and specificity as lincomycin. Lipophilic S ‐uloside analogues were two‐ to fourfold less active than the parent antibiotic, whilst the hydrophilic analogues were inactive.