The total synthesis of (+)-milbemycin β₃

Abstract

We report the total synthesis of (+)-milbemycin p3 from the optically pure precursors spiroacetal (3) and vinyl iodide (Z), and the aromatic aldehyde (4).The milbemycins comprise a group of natural products isolated from cultures of Streptomyces B-41-146, of which milbemycin p3 (1) is the simplest.1 Interest in these compounds has increased since the isolation and identification of a structurally related series of macrolides, the avermectins.'

Uncatalyzed reactions of 4,4′-diphenylmethane-diisocyanate with polymer polyols as revealed by matrix-assisted laser desorption/ionization mass spectrometry

“…[1][2][3] PUs have recently received considerable attention as shape-memory materials. [7][8][9][10] The kinetic studies on this topic have primarily focused on the reactions of mono-and industrially important diisocyanates with monofunctional alcohols to obtain the reaction order for both the isocyanate and alcohol components and to establish the reaction mechanism. Proper selection of the isocyanate and the polyol components allows one to tailor the properties of the resulting PUs for various applications.…”

Preparation of chiral lactone from laevoglucosan; a key intermediate for synthesis of the spiroacetal moieties of the avermectins and milbemycins

“…The resin was then filtered off and the solvent removed at reduced pressure. Flash chromatography (ether) afforded the title compounds (14).-The methyl glycoside (13) (5 g, 146 mmol) was dissolved in THF (60 ml) and l~ hydrochloric acid (5 ml) added; further THF was added until the mixture appeared homogenous (ca. 20 ml).…”

De novo synthesis of natural products via the asymmetric hydration of polyenes

“…40 Pharmacological interest in the milbemycins reemerged after it was discovered that they are also potent efflux pump inhibitors. 41 Several methods of total syntheses to milbemycin β 3 have been reported, 42 although until this work none of the routes established the asymmetric of the natural product via asymmetric catalysis. Thus we were inspired to try to develop a de novo asymmetric approach using our asymmetric hydration strategy.…”

“…Finally, with all the chiral centers established in aldehyde 45 , it was stereoselectively converted into the E , E -diene 46 . Building upon the precedent from the Barrett and Smith previous syntheses, 42e,g 46 was converted into natural product milbemycin β 3 (Scheme 9). This invloved silyl ether removal (TBAF), methyl ester hydrolysis, macrolactonization (DIAD/PPh 3 ) followed by deprotection of the methyl group.…”