19 AN ATTEMPTED TOTAL SYNTHESIS OF TETRODOTOXINE FROM D-GLUCOSE
Details
A synthetic plan of tetrodotoxin from D-glucose was made and its key-problems were previously examined. The plan is roughly composed of (1) introduction of hydroxymethyl group at C_3 of D-glucose, (2) introduction of a protected aldehyde or an equivalent group instead of the C_5-hydroxyl group, (3) conversion of C_6-hydroxyl group to nitro group and followed by cyclization between C_1 and C_6, (4) condensation of glyoxylic acid at the position of nitro group of the resulted nitro-cyclohexanol, and (5) conversion of the nitro group to guanidine group and followed by cyclization with the aldehyde group protected, and following results were obtained for these problems. (1) 1, 2;5, 6-Di-O-isopropylidene-3-C-hydroxymethyl-α-D-glueofuranose (13) was successfully obtained by condensation of 1, 2;5, 6-di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose with diazomethane and followed by treatment with alkali, or by treatment of the corresponding 3-C-methylene derivative with permanganate, and the configuration at C_3 of 13 was throughly proved. (2 and 3) Introduction of nitromethyl group at C_5 was accomplished by reaction of nitromethane with 3-O-benzyl-1, 2-O-isopropylidene-6-O-trityl-α-D-xylo-hexofuranos-5-ulose or 3-O-acetyl-5, 6-dideoxy-1, 2-O-isopropylidene-6-C-nitro-α-D-xylo-hexofurano-5-enose as model compounds, and cyclization of them are now undertaking. (4 and 5) The facts that glyoxylic acid condensed with 2-nitrocy-clohexanol and that 2-deoxy-2-guadidino-D-glucose exists as D-glucofurano[1', 2';4, 5]-2-imino-imidazolidine or 2-imino-4-(D-arabo-tetrahyd-roxybutyl)-imidazole supported the above mentioned plan.
