Sato Ken-ichi, Akai Shoji, Sugita Naoki, Ohsawa Tadatsugu, Kogure Tomokazu, Shoji Hirotsugu, Yoshimura Juji
Laboratory of Organic Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1, Rokkakubashi, Kanagawa-ku, Yokohama, 221-8686 Japan.
J Org Chem. 2005 Sep 16;70(19):7496-504. doi: 10.1021/jo050342t.
[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.
