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Antibiotics from Gliding Bacteria, LIX. Disorazoles, Highly Cytotoxic Metabolites from the Sorangicin‐Producing Bacterium Sorangium Cellulosum , Strain So ce12
Author(s) -
Jansen Rolf,
Irschik Herbert,
Reichenbach Hans,
Wray Victor,
Höfle Gerhard
Publication year - 1994
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199419940802
Subject(s) - chemistry , stereochemistry , hydroxylation , ether , bacteria , methyl group , epoxide , amino sugar , organic chemistry , group (periodic table) , catalysis , enzyme , genetics , biology
Twenty‐nine disorazoles A–H ( 1–29 ) were isolated by solvent partitions and chromatographic separations from Sorangium cellulosum , strain So ce12, the producer of the sorangicin antibiotics. The disorazoles proved to be highly cytotoxic and active against fungi. The structures of the main component disorazole A 1 ( 1 ) and 28 variants were elucidated by 2D‐NMR and mass spectroscopy. The disorazoles are macrocyclic dilactones of two 2‐pentadecyloxazol‐4‐carboxylic acids, which are modified in their carbon chain by variation of the position and configuration of double bonds and oxygen substituents like epoxide, hydroxyl, or methyl ether groups. In addition to these, three disorazoles are ring‐enlarged by lactonization to a more distant hydroxyl group. By feeding of 13 C‐enriched precursors the biosynthetic origin of the carbons in disorazole A ( 1 ) was investigated. C‐2 of the oxazole and the attached pentadecyl chain arise from acetate. The geminal methyl groups and the methoxyl group are derived from the methyl group of methionine.