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Sannamycin‐type aminoglycoside antibiotics of natural and non‐natural (mirror‐image) configuration — total syntheses and biological activity
Author(s) -
Ludin Christian,
Weller Thomas,
Seitz Bernhard,
Meier Walter,
Erbeck Silke,
Hoenke Christoph,
Krieger Richard,
Keller Manfred,
Knothe Lothar,
Pelz Klaus,
Wittmer Annette,
Prinzbach Horst
Publication year - 1995
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.199519950239
Subject(s) - diastereomer , chemistry , enantiomer , anomer , glycoside , stereochemistry , glycosyl , glycosylation , stereoisomerism , organic chemistry , catalysis , biochemistry
Sets of variously protected purpurosamine/2‐ epi ‐purpurosamine‐type glycosyl donors ( O ‐acetates) and sannamine‐type glycosyl acceptors were coupled as racemates and pure enantiomers, according to a modified Koenigs‐Knorr procedure with TMSOTf as promotor. The α anomers isolated from the respective mixtures of glycosides (yields varying between 51% and 91%, α:β anomeric ratios between 1.5:1 and 13:1, α:α′ diastereomeric ratios between 1:1 and 1:1.5) were transformed through standard protection/deprotection and glycidation measures into 6′‐des( N ‐methyl)sannamycins A ( 1, 1′, 2, 2′ ) and B ( 37, 37′ ), 2′‐ epi ‐6′‐des( N ‐methyl)sannamycins ( 3, 3′ ), the enantiomeric sannamycins A and B ( ent ‐ 4 )/ ( ent ‐ 40 ), the diastereomers ( ent ‐ 4′ )/( ent ‐ 40′ ), and the enantiomeric 2′‐ epi ‐sannamycin A ( ent ‐ 5 )/( ent ‐β‐ 5 ). For one of the fluorinated glycosides (α‐ 26′ ), featuring a somewhat unusual aglycon conformation, an X‐ray structural analysis was performed. In explorative biological tests, the naturally configurated glycosides 1 and 3 showed limited, 2 a rather broad activity against a number of pathogenic microorganisms. Yet, none of the glycosides with non‐natural configuration was found to be active.