81(P71) シガトキシンの絶対構造の決定と新規同族体の単離(ポスター発表の部)

抄録

Ciguatoxin (1) is the principal toxin of the seafood poisoning, which is termed ciguatera and is prevalent in tropical and subtropical areas. The toxin structure including the relative stereochemistry was determined using NMR methods by our group. However, configurations at C2 and C5 remained undetermined due to the extrmely low amount of 1. In order to determine the absolute configuration at C2, we protected 1,2-diol of CTX and then cleaved the 3,4-double bond by osmium oxidation followed by NaBH_4 reduction. The resultant alcohol was esterified with a chiral fluorometric reagent (S)-(+)-2-tert-butyl-2-methyl-1,3-benzodioxo-le-4-carboxylic acid and compared with synthetic references on two HPLC systems. Starting with only 5μg of 1 the absolute configuration at C2 was successfully determined to be S. To determine the absolute configuration at C5, 100μg of CTX4A was reacted with ρ-bromobenzoyl chloride to yield tris-bromobenzoyl derivative. The CD spectrum of CTX4A-tris-ρ-bromobenzoate was comparable with that of ρ-bromobenzoate derived from a synthetic (5R) AB fragment. This result indicated that the absolute configuration at C5 is R. Consequently, determining (2S), (5R) configuration allowed us to assign whole stereostructure of 1. A new ciguatoxin analog, CTX2A1 (2), isolated from moray eels was deduced to have the molecular formula C_<57>H_<84>O_<18> from FABMS. The structure of 2 was elucidated to be CTX3C-2,3-diol by detailed analysis of NMR spectra. This is the first CTX analog to be oxidised in the A ring and is an additional example to show diverse metabolic modification of CTXs to occur in fish.