Total synthesis of nhatrangin A.
A concise and stereoselective approach for the synthesis of key intermediates for aplysiatoxins, oscillatoxins, and nhatrangins and their utility for the total synthesis of nhatrangin A has been demonstrated. The advanced intermediates aromatic aldehyde 11 and dihydroxy acid 12 were synthesized in eight steps (44% overall yield) and three steps (55% overall yield), respectively. An asymmetric Michael addition, CBS reduction, and proline-catalyzed crossed-aldol reactions were utilized as key steps for the generation of all the chirality of main chain hydroxyaldehyde, while the appended side-chain-protected 3,4-dihydroxypentanoic acid was achieved in a shortest route, using Sharpless dihydroxylation, diol protection, and RuO4-catalyzed aromatic over-oxidation reactions. Synthesis of nhatrangin A was accomplished by coupling of dihydroxy acid 12 with β-hydroxyallyl ester (obtained from 11) under Yamaguchi reaction conditions followed by a one-pot deprotection of all protecting groups.
Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. yadavpub@iict.res.in
Jhillu Singh
JS
Yadav
Goreti
G
Rajendar
Ramisetti Srinivasa
RS
Rao
Srihari
S
Pabbaraja
D008235:Lyngbya Toxins / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation
D008235:Lyngbya Toxins; C549735:nhatrangin A