Efficient Total Syntheses of Resin Glycosides and Analogues by Ring-Closing Olefin Metathesis

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Abstract

A highly efficient entry into the resin glycoside family of natural products is outlined which takes advantage of the inherently modular character of ring-closing metathesis (RCM) for the formation of their macrolactone substructures. Starting from only three well accessible sugar building blocks and (6S)-undec-1-en-6-ol (7) (prepared by enantioselective addition of dipentylzinc to hexenal in the presence of a catalyst formed from Ti(OiPr)4 and bis-(R,R)-trifluoromethanesulfonamide (9)), it was possible to achieve total syntheses of tricolorin A (1), tricolorin G (2), and jalapinolic acid (58) as well as the synthesis of the disaccharidic unit 48 which constitutes a common structural motif of all simonin, operculin, tuguajalapin, orizabin, mammoside, quamoclin, and stoloniferin resin glycosides. Furthermore, various analogues of these naturally occurring glycolipids have been obtained in a straightforward manner from the same set of substrates. This highlights the flexibility of the chosen approach and opens the door for a synthesis-driven mapping of the structure/activity profile of this structurally demanding class of oligosaccharides. The macrocyclization reactions via RCM have been performed using carbene 22 introduced by Grubbs, the cationic allenylidene complex 23, or the particularly convenient precatalyst [(p-cymene)RuCl2(PCy3)] 24. All these ruthenium-based systems catalyze the ring closure of the highly functionalized diene substrates with comparable efficiency and turned out to be compatible with an array of functional groups including unprotected secondary hydroxyl functions.

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