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Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition–cyclization strategy: Synthesis of (-)-flustramine B

Austin, Joel F. and Kim, Sung-Gon and Sinz, Christopher J. and Xiao, Wen-Jing and MacMillan, David W. C. (2004) Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition–cyclization strategy: Synthesis of (-)-flustramine B. Proceedings of the National Academy of Sciences of the United States of America, 101 (15). pp. 5482-5487. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:AUSpnas04

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Abstract

Pyrroloindoline and bispyrroloindoline are a subclass of alkaloid structural motifs that commonly exhibit biological activity. An enantioselective organocatalytic approach to the synthesis of pyrroloindoline architecture is described. The addition–cyclization of tryptamines with {alpha},{beta}-unsaturated aldehydes in the presence of imidazolidinone catalysts 1 and 8 provides pyrroloindoline adducts in high yield and excellent enantioselectivities. This transformation is successful for a wide range of tryptamine and {alpha},{beta}-unsaturated aldehyde substrates. This amine-catalyzed sequence has been extended to the enantioselective construction of furanoindoline frameworks. Application of this pyrroloindoline-forming reaction to natural product synthesis has been accomplished in the context of the enantioselective synthesis of (–)-flustramine B.


Item Type:Article
Additional Information:Copyright © 2004 by The National Academy of Sciences. This paper was submitted directly (Track II) to the PNAS office. Edited by Jack Halpern, University of Chicago, Chicago, IL, and approved February 23, 2004 (received for review December 12, 2003). Published online before print April 5, 2004, 10.1073/pnas.0308177101 From the Cover: Asymmetric Catalysis Special Feature Part I. We thank Dr. Claudia Roberson for insightful discussions and Dr. Larry Henling and Dr. Michael Day for x-ray crystallographic analysis. This work was supported by National Institute of General Medical Sciences Grant R01 GM66142-01 and kind gifts from Bristol-Myers Squibb, Johnson and Johnson, Eli Lilly, and Merck Research Laboratories. D.W.C.M. was supported by the Camille and Henry Dreyfuss Foundation and the Sloan Foundation and Research Corporation under the Cottrell Scholarship and Research Innovation programs. J.F.A. received a graduate fellowship from the Fannie and John Hertz Foundation, S.-G.K received postdoctoral fellowship support from Korean Science and Engineering Foundation, and C.J.S. received postdoctoral fellowship support from National Institutes of Health Grant 1-F32-CA91635-01. Data deposition: The atomic coordinates have been deposited in the Cambridge Structural Database, Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, United Kingdom (CSD reference nos. 197024 and 234570).
Record Number:CaltechAUTHORS:AUSpnas04
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:AUSpnas04
Alternative URL:http://dx.doi.org/10.1073/pnas.0308177101
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:635
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:08 Sep 2005
Last Modified:26 Dec 2012 08:40

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