The concise total synthesis of marine alkaloids, (-)-flustramines A and B, and (-)-flustramides A and B has been achieved through the domino olefination/isomerization/Claisen rearrangement (OIC) for highly enantioselective construction of the asymmetric quaternary carbon center and the chemoselective reduction-cyclization (RC) for pyrrolidine formation as key steps.

Here we describe the efficient total synthesis of the three title hexahydropyrrolo[2,3-b]indole alkaloids and debromo derivative from readily available indolin-3-ones using key domino reactions, olefination-isomerization-Claisen rearrangement (OIC), and reductive cyclization (RC). (+/-)-Flustramine C (5) was synthesized in five steps from 6-bromoindolin-3-one 9 via a key intermediate 13a. (+/-)-Flustramine A (1) has been obtained by reduction of flustramide A (6), which has been prepared in five steps from 13a. (+/-)-Debromoflustramine A (19) was provided in a similar manner from 13b. The (-)- and (+)-enantiomers of 19 were synthesized through optical resolution of (+/-)-carboxylic acid 17b using (R)-4-phenyloxazolidin-2-one.

Enantioselective Total Synthesis of (-)-Flustramines A, B and (-)-Flustramides A, B via Domino Olefination/Isomerization/Claisen RearrangementSequence. -The natural compounds (V) and (VI) are synthesized via the title domino and chemoselective reduction-cyclization process as key steps. -(KAWASAKI*, T.; SHINADA, M.; KAMIMURA, D.; OHZONO, M.; OGAWA, A.; Chem. Commun. (Cambridge) 2006, 4, 420-422; Meiji Pharm. Univ., Kiyose, Tokyo 204, Japan; Eng.) -K. Schneider 21-188

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