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Antibiotics from gliding bacteria, LXV . Synthesis of soraphen analogues by substitution of the phenyl‐C‐17 ring segment of soraphen A 1α
Author(s) -
Schummer Dietmar,
Jahn Thorsten,
Höfle Gerhard
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.1995199505118
Subject(s) - chemistry , substituent , lactone , stereochemistry , moiety , ring (chemistry) , aldehyde , cleavage (geology) , organic chemistry , catalysis , geotechnical engineering , fracture (geology) , engineering
The partial synthesis of 11 analogues of soraphen A 1α ( 1 ) is described. Reductive lactone ring cleavage, transformation into (17 R,S )‐soraphenic acid 10 and cyclization provided unnatural 17‐epi‐soraphen A 1α ( 12 ). Removal of the phenyl‐C‐17 ring segment of 1 by cleavage of the lactone moiety and the C‐16/C‐17 bond gave the aldehyde 16 as central intermediate. After homologation of 16 , introduction of a new C‐17 substituent R or H, and cyclization of the lactone ring, the soraphen analogues butyl‐, thienyl‐, and tolylsoraphen 2b, d, e and 22b, d, e and the desphenylsoraphen 2a were obtained. The ring‐contracted soraphen analogues norsoraphen 29 and 30 and desphenylnorsoraphen 31 were synthesized by introduction of a phenyl group or reduction of the intermediate aldehyde 23 followed by cyclization to the lactone. The biological activity of the soraphen analogues against Candida albicans was determined. Compared to the natural product, all analogues exhibit reduced activity. The activity of the analogues strongly depends upon the nature of the substituent R, the configuration at C‐17, and the ring size.