SYNTHESIS OF NEW ANALOGS OF ECHINOCANDIN B BY ENZYMATIC DEACYLATION AND CHEMICAL REACYLATION OF THE ECHINOCANDIN B PEPTIDE: SYNTHESIS OF THE ANTIFUNGAL AGENT CILOFUNGIN (LY121019)

M. DEBONO; B. J. ABBOTT; D. S. FUKUDA; M. BARNHART; K. E. WILLARD; R. M. MOLLOY; K. H. MICHEL; J. R. TURNER; T. F. BUTLER; A. H. HUNT

doi:10.7164/antibiotics.42.389

M. DEBONO, B. J. ABBOTT, D. S. FUKUDA, M. BARNHART, K. E. WILLARD, R. M. MOLLOY, K. H. MICHEL, J. R. TURNER, T. F. BUTLER, A. H. HUNT

Author information

M. DEBONO
Lilly Research Laboratories, Eli Lilly and Company
B. J. ABBOTT
Lilly Research Laboratories, Eli Lilly and Company
D. S. FUKUDA
Lilly Research Laboratories, Eli Lilly and Company
M. BARNHART
Lilly Research Laboratories, Eli Lilly and Company
K. E. WILLARD
Lilly Research Laboratories, Eli Lilly and Company
R. M. MOLLOY
Lilly Research Laboratories, Eli Lilly and Company
K. H. MICHEL
Lilly Research Laboratories, Eli Lilly and Company
J. R. TURNER
Lilly Research Laboratories, Eli Lilly and Company
T. F. BUTLER
Lilly Research Laboratories, Eli Lilly and Company
A. H. HUNT
Lilly Research Laboratories, Eli Lilly and Company

JOURNAL FREE ACCESS

1989 Volume 42 Issue 3 Pages 389-397

DOI https://doi.org/10.7164/antibiotics.42.389

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Abstract

The antifungal antibiotic, echinocandin B (ECB), was modified by a sequential procedure in which the initial step involved enzymatic removal of the native N-linoleoyl group from the N-terminus using an Actinoplanes utahensis culture. The resulting product, ECB nucleus, was reacylated using active esters or acid halides of various substituted acids to give a series of ECB analogs. These analogs possessed anti-Candida activity both in vitro and in vivo (mice). Other studies have shown that one of these, cilofungin, the 4-n-octyloxybenzoyl-ECB analog (LY121019), has excellent anti-Candida activity, low toxicity and is superior to other available antifungal antibiotics.

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