Novel and stereocontrolled synthesis of (+/-)-tetrodotoxin from myo-inositol.
[reactions: see text] The novel and stereocontrolled synthesis of (+/-)-tetrodotoxin from myo-inositol is described. The key steps involve the stepwise oxidation of hydroxyl groups to the carbonyl function, followed by the addition of specific nucleophiles, including the successive spiro alpha-chloroepoxide formation and its ring-opening with the azide anion, to give the desired branched chain structures (5-->6, 17-->18-->19-->20 and 23-->24-->25) with the desired regio- and stereoselectivities in high yields. The stepwise conversion of the alpha-azido aldehyde 25 to the delta-lactone 29, followed by reduction of the azide, introduction of a guanidine moiety, aldehyde formation, and deprotection, produced the (+/-)-tetrodotoxin.
Sato
Ken-ichi
K
Laboratory of Organic Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1, Rokkakubashi, Kanagawa-ku, Yokohama, 221-8686 Japan. satouk01@kanagawa-u.ac.jp
Akai
Shoji
S
Sugita
Naoki
N
Ohsawa
Tadatsugu
T
Kogure
Tomokazu
T
Shoji
Hirotsugu
H
Yoshimura
Juji
J
D013237:Stereoisomerism; D013779:Tetrodotoxin / Q000138:chemical synthesis*
D013779:Tetrodotoxin