Avermectins and milbemycins Part I

New Milbemycins from Streptomyces hygroscopicus subsp. aureolacrimosus. Fermentation, Isolation and Structure Elucidation.

“…Position a2Q(l) a2l (2) a22 (3) a23 (4) a24 (5) a25 (6) a26 (7) a27 (8) & (9) £10 (10) 13C-NMR spectra for milbemycins a20 (1) and a2l (2) were measured at 50 MHz. 13C-NMR spectra for milbemycins a22 (3), a23 (4), a24 (5), a25 (6), a26 (7), a27 (8), /39 (9), /310 (10), J3n (ll), and /312 (12) were measured at 67.5 MHz.…”

“…A portion of spore suspension or a loopful of mature spores from the slant culture was inoculated into a 500-ml Erlenmeyer flask containing 50 ml of seed medium. After cultivating for 3 days at 28°C on a rotary shaker, 1 ml of the seed culture was transferred into a 100-ml Erlenmeyer flask containing 15ml of the production medium, TY- [1][2][3] (sucrose 12%, Pharmamedia® 1.1%, soybean meal 1.1%, skim milk 1.1%, K2HPO4 0.1%, FeSO4-7H2O 0.01%, CaCO3 0.25%, pH 7.2). The cultivation was continued for 1 1 days at 28°C on a rotary shaker.…”

“…Fermentation Process A for the Production of Metabolites [1][2][3][4] For the first stage preculture, 2ml of spore suspension was inoculated into 550ml of PS medium contained in a 2-liter Erlenmeyer flask. The inoculated flask was incubated on a rotary shaker at 28°C for 2 days.…”

Research and Development of Macrocyclic Compounds as Fungicides

“…Naturally occurring macrocyclic compounds, especially macrolactam and macrolactone have attracted considerable interest of chemists and the natural products community because they display a diverse range of biological activity including pesticidal activity. Several examples include avermectins, a group of 16-membered ring lactones with anthelmintic, insecticidal and acaricidal activities (Fisher, 1990 andGreen, 1991), spinosyns, a group of 12-membered ring lactones with insecticidal activity (Sparks et al, 1998;Crouse et al, 2001), epilachnene, a kind of structurally novel azamacrolide with antifeedant activity (Attygalle et al, 1993), pyrenophorol, a macrodiolide with herbicidal activity (Kastanise and Chrysayi-Tokousbalides, 2000), and maltophilin, a novel macrolactam, produced by strains of Stenotrophomonas maltophilia R3089 isolated from the rhizosphere of rape plants (Brassica napus L.), which exhibited biological activity against a broad spectrum of fungi (Jakobi et al, 1996). This chapter will describe the discovery of fungicidal novel lead compounds, especially those macrocyclic compounds which have relative simple structure and can be synthesized easily from readily available raw materials, by mimicking the structure of natural occurring macrolactone and macrolactam, and the development of the compounds with high fungicidal activity.…”

Milbemycin derivatives: Epoxidation of milbemycins.

“…8,14,8,[9][10][11][12][13][14]and 3,[4][5][6][7][8][9][10][11][12][13][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.…”