Milbemycin derivatives: epoxidation of milbemycins.
Epoxidation reactions (MCPBA epoxidation and Sharpless epoxidation) were examined as a means of chemically modifying milbemycins as part of our program for discovering anthelmintics. 8,9-Epoxy-, 14,15-epoxy-, 8,9-14,15-diepoxy-, and 3,4-8,9-14,15-triepoxymilbemycin A4 were selectively obtained from milbemycin A4 and its derivatives, in which either the C-5 and C-7 hydroxyl groups or C-5 alone were protected as appropriate by a silyl ether (in the former case) or a carbonyl group. Further silylation or epoxidation on these epoxidized compounds indicated that the configuration of each epoxide moiety of the mono- and diepoxides is in accord with that of the corresponding epoxide moiety of the triepoxide. Furthermore, in order to confirm the absolute configurations of these epoxide functionalities, an X-ray analysis of a carbamate derivative from the triepoxymilbemycin was conducted.
Naito
S
S
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Saito
A
A
Furukawa
Y
Y
Hata
T
T
Nakada
Y
Y
Muramatsu
S
S
Ide
J
J
D000871:Anthelmintics / Q000737:chemistry* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification; D002723:Chlorobenzoates / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry* / Q000302:isolation & purification; D018942:Macrolides; D015394:Molecular Structure; D013237:Stereoisomerism
D000871:Anthelmintics; D000900:Anti-Bacterial Agents; D002723:Chlorobenzoates; D004852:Epoxy Compounds; D018942:Macrolides; C000433:3-chloroperbenzoic acid; C027837:moxidectin