The synthesis of pseudomycin C' via a novel acid promoted side-chain deacylation of pseudomycin A.
The gamma hydroxyl present in the aliphatic side chain of the natural products pseudomycin A and C' provided a unique handle for the pH dependent side-chain deacylation. Low pH reaction conditions were used to cleave the side chain with minimal degradation of the peptide core. The pseudomycin nucleus intermediate obtained from the deacylation of pseudomycin A was pivotal in the synthesis of novel side-chain analogues. A practical synthesis of a minor fermentation factor pseudomycin C' and related analogues is reported.
Rodriguez
M J
MJ
Lilly Research Laboratories, A Division of Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. mjrodriguez@lilly.com
Belvo
M
M
Morris
R
R
Zeckner
D J
DJ
Current
W L
WL
Sachs
R K
RK
Zweifel
M J
MJ
D000215:Acylation; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D006658:Histoplasma / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D023421:Models, Animal; D009181:Mycoses / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015996:Survival Rate
D000935:Antifungal Agents; D010456:Peptides, Cyclic; C107665:pseudomycin A