Synthesis and antifungal activity of C-16 oximino and vinyl amphotericin B derivatives.
Several new C-16 oximino and vinyl derivatives of amphotericin B are described. They are prepared by the reaction of a suitably protected amphotericin B C-16 aldehyde with hydroxylamine derivatives and Wittig reagents, respectively, followed by sequential removal of the protecting groups. The compounds possess potent antifungal activity in vitro, similar to or in some cases superior to that of amphotericin B itself. With the exception of the C-16 (Z)-methoxime, the new derivatives do not show significantly reduced haemolytic activity against mammalian erythrocytes compared with amphotericin B.
Corbett
D F
DF
SmithKline Beecham Pharmaceuticals, Epsom, Surrey, UK.
Dean
D K
DK
Greenlees
A R
AR
Macpherson
D T
DT
D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D004912:Erythrocytes / Q000187:drug effects; D006736:Horses; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use
D010091:Oximes; D014753:Vinyl Compounds; D000666:Amphotericin B