Total Synthesis of Tricolorin A.

Tricolorin A (1) is a novel tetrasaccharide macrolactone that is a natural herbicide. In this paper is reported a total synthesis of 1. Coupling of hydroxy ester 18 with D-fucosyl trichloroacetimidate 23 gave fucoside 24. Removal of the C-2 pivaloyl group of 24 followed by coupling with D-glucosyl trichloroacetimidate 29 resulted in isolation of disaccharide 30. Saponification of the ester groups of 30 and subsequent selective macrolactonization of the acid diol 31 by the Yonemitsu protocol gave only the desired lactone 32. The key step in the assembly of disaccharide glycosyl trichloroacetimidate 52 was coupling L-rhamnoside 47 with L-rhamnosyl trichloroacetimidate 43. Attempts to couple lactone disaccharide 32 with disaccharide 52 were unsuccessful. Using an alternate plan for assembly of the tetrasaccharide, reaction of disaccharide glycosyl trichloroacetimidate 58 with disaccharide 37 gave tetrasaccharide 59. Diester lactone 63 was generated by selective macrolactonization of tetrasaccharide acid triol 60, again using the Yonemitsu protocol, followed by addition of the chiral side chain acid to the reaction vessel. Synthetic tricolorin A (1) was obtained by deprotection of 63. Starting from fucose, glucose, rhamnose, and (S)-1-octyn-3-ol, the synthesis required 39 steps overall. The longest linear sequence was 14 steps, with an overall yield for this longest linear sequence of 6%.