Novel and Stereocontrolled Synthesis of (.+‐.)‐Tetrodotoxin (I) from myo‐Inositol.

Abstract

Carbohydrates U 0500Novel and Stereocontrolled Synthesis of (±)-Tetrodotoxin (I) from myo-Inositol. -(SATO*, K.-I.; AKAI, S.; SUGITA, N.; OHSAWA, T.; KOGURE, T.; SHOJI, H.; YOSHIMURA, J.; J.

Total Synthesis of Tetrodotoxin and 9-epiTetrodotoxin

“…To date, numerous efforts have been made towards the total synthesis of TTX, with the first synthesis by Kishi in 1972. 15,16 Subsequently, asymmetric syntheses have been achieved by Isobe, 8,17 Du Bois, 18 Sato, [19][20][21] Fukuyama, 22 Yokoshima, 23 and Marin. 24 More recently, Trauner described an elegant and concise asymmetric synthesis of TTX based on a glucose derivative.…”

“…Precise functional group manipulations on heavily heteroatom-substituted, stereochemically complex frameworks have proven challenging, as evidenced by the total synthesis of highly oxidized natural products, [45][46][47][48][49][50][51][52][53] and as exemplified by the synthetic studies of TTX by Isobe, 8 Du Bios, 18 Sato, 19,20 Yokoshima, 23 and Trauner 25 (Figure 1) using highly oxygenated natural starting materials such as, D-glucose (2), myo-inositol (3), D-mannoside (4), or D-isoascorbic acid (5). Although the preexisting oxygen functionality in these naturally occurring materials provides the functionality basis of TTX, efficient and precise interconversion of these similar functionalities on the densely heteroatom-substituted skeleton in a chemo and stereoselective manner is arduous.…”

Total Synthesis of Tetrodotoxin and 9-epiTetrodotoxin

“…To date, numerous efforts have been made towards the total synthesis of TTX, with the rst synthesis by Kishi in 1972. 15,16 Subsequently, asymmetric syntheses have been achieved by Isobe, 8,17 Du Bois, 18 Sato, [19][20][21] Fukuyama, 22 Yokoshima, 23 and Marin. 24 More recently, Trauner described an elegant and concise asymmetric synthesis of TTX based on a glucose derivative.…”

“…Precise functional group manipulations on heavily heteroatom-substituted, stereochemically complex frameworks have proven challenging, as evidenced by the total synthesis of highly oxidized natural products, [45][46][47][48][49][50][51][52][53] and as exempli ed by the synthetic studies of TTX by Isobe, 8 Du Bios, 18 Sato, 19,20 Yokoshima, 23 and Trauner 25 (Figure 1) using highly oxygenated natural starting materials such as, Dglucose (2), myo-inositol (3), D-mannoside (4), or D-isoascorbic acid (5). Although the preexisting oxygen functionality in these naturally occurring materials provides the functionality basis of TTX, e cient and precise interconversion of these similar functionalities on the densely heteroatom-substituted skeleton in a chemo and stereoselective manner is arduous.…”