The total synthesis of tricolorin A

Tricolorin A (4) is a novel tetrasaccharide macrolactone that is a natural herbicide. In this dissertation is reported a total synthesis of 4. Coupling of hydroxy ester 58 with sc D-fucosyl trichloroacetimidate 113 gave fucoside 100. Removal of the C-2 pivaloyl group of 100 followed by coupling with sc D-glucosyl trichloroacetimidate 135 resulted in isolation of disaccharide 136. Saponification of the ester groups of 136 and subsequent selective macrolactonization of the acid diol 137 by the Yonemitsu protocol gave only the desired lactone 138. The key step in the assembly of disaccharide glycosyl trichloroacetimidate 155 was coupling sc L-rhamnoside 150 with sc L-rhamnosyl trichloroacetimidate 28. Attempts to couple lactone disaccharide 138 with disaccharide 155 were unsuccessful. Using an alternate plan for assembly of the tetrasaccharide, reaction of disaccharide glycosyl trichloroacetimidate 165 with disaccharide 143 gave tetrasaccharide 166. Diester lactone 168 was generated by selective macrolactonization of tetrasaccharide acid triol 162, again using the Yonemitsu protocol, followed by addition of the chiral side chain acid to the reaction vessel. Synthetic tricolorin A (4) was obtained by deprotection of 168. 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%.