The total synthesis of the noncyanogenic cyanoglucoside 1, originally isolated from Ilex warburgii, was achieved in nine steps (9% overall yield), starting from an optically pure Diels-Alder adduct ((+)-3). The key step of the synthesis, the glycosidation, was carried out under Koenigs-Knorr conditions closely related to those developed for the total syntheses of (À)-lithospermoside and (À)-bauhinin. We had to tune the protecting groups used for the two free cis-configured OH groups of the aglycone, which afforded the desired b-D-glucoside intermediate 15 in very good yield (62%). Introduction. -The noncyanogenic cyanoglucoside 1 (= (2Z)-[(4R,5R,6S)-6-(b-Dglucopyranosyloxy)-4,5-dihydroxycyclohex-2-en-1-ylidene]ethanenitrile) [1] was first isolated in 1983 by Ueda and co-workers [1a] from the fruit of Ilex warburgii, an endemic plant growing in Iriomote Island (southern part of the Ryukyu Islands, Okinawa, Japan). The berries of I. warburgii were also found to contain (À)-menisdaurin (2) [2], another noncyanogenic cyanoglucoside, which had been isolated before in 1978 from Menispermum dauricum [2a]. Regarding the structure of 1, it is noteworthy that the three OH functions of the aglycone have the 4,5,6-cis relative configuration [1].
A number of other noncyanogenic cyanoglucosides of related structure, e.g., lithospermoside, dasycarponin, bauhinin, and purshianin, have been isolated from various medicinal plants [3]. Therefore, they appear to be interesting targets for total synthesis, as numerous other natural glycosides [4]. Herein, we report the first total synthesis of compound 1. The versatility of our glycosidation conditions developed during the syntheses of (À)-bauhinin and (À)-lithospermoside [5] allowed us to prepare the desired b-D-glucoside with the unusual all-cis relative configuration.