Synthesis and antifungal selectivity of new derivatives of amphotericin B modified at the C-13 position.
The syntheses of the first amphotericin B derivatives to be modified solely at the C-13 hemiketal position are described. Selective functionalisation at this position is facilitated by use of the allyl ester as a C-16 carboxylate protecting group on the amphotericin B nucleus. In in vitro tests all compounds showed markedly reduced haemolytic activity against mammalian erythrocytes while two of the novel 13-alkoxy derivatives retained good antifungal activity.
Taylor
A W
AW
SmithKline Beecham Pharmaceuticals, Great Burgh, Epsom, Surrey, UK.
Costello
B J
BJ
Hunter
P A
PA
MacLachlan
W S
WS
Shanks
C T
CT
D000666:Amphotericin B / Q000031:analogs & derivatives*; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D006736:Horses; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D000666:Amphotericin B