Catalyst-Controlled Stereoselective Synthesis Secures the Structure of the Antimalarial Isocyanoterpene Pustulosaisonitrile-1

White, Andrew M., Dao, Kathy, Vrubliauskas, Darius, Könst, Zef A., Pierens, Gregory K., Mándi, Attila, Andrews, Katherine T., Skinner-Adams, Tina S., Clarke, Mary E., Narbutas, Patrick T., Sim, Desmond C.-M., Cheney, Karen L., Kurtán, Tibor, Garson, Mary J. and Vanderwal, Christopher D. (2017) Catalyst-Controlled Stereoselective Synthesis Secures the Structure of the Antimalarial Isocyanoterpene Pustulosaisonitrile-1. Journal of Organic Chemistry, 82 24: 13313-13323. doi:10.1021/acs.joc.7b02421


Author White, Andrew M.
Dao, Kathy
Vrubliauskas, Darius
Könst, Zef A.
Pierens, Gregory K.
Mándi, Attila
Andrews, Katherine T.
Skinner-Adams, Tina S.
Clarke, Mary E.
Narbutas, Patrick T.
Sim, Desmond C.-M.
Cheney, Karen L.
Kurtán, Tibor
Garson, Mary J.
Vanderwal, Christopher D.
Title Catalyst-Controlled Stereoselective Synthesis Secures the Structure of the Antimalarial Isocyanoterpene Pustulosaisonitrile-1
Journal name Journal of Organic Chemistry   Check publisher's open access policy
ISSN 1520-6904
0022-3263
Publication date 2017-11-10
Year available 2017
Sub-type Article (original research)
DOI 10.1021/acs.joc.7b02421
Open Access Status Not yet assessed
Volume 82
Issue 24
Start page 13313
End page 13323
Total pages 11
Place of publication Washington, DC United States
Publisher American Chemical Society
Language eng
Subject 1605 Organic Chemistry
Abstract Three new isocyanoditerpenes (5-7) have been characterized from Australian specimens of the nudibranch Phyllidiella pustulosa. The planar structure and (3R,6S,7R) absolute configuration of pustulosaisonitrile-1 were deduced by spectroscopic analyses at 900 MHz informed by molecular modeling, DFT calculations, and computational NMR chemical shift predictions and by comparison of experimental electronic circular dichroism (ECD) data with TDDFT-ECD calculations for the truncated model compound 8. A catalyst-controlled enantio- and diastereoselective total synthesis of the two most likely diastereomeric candidates for the structure of 5 solidified its (3R,6S,7R,10S,11R,14R) absolute configuration. Three individual enantioselective methods provided stereochemical control at key positions, permitting an unambiguous final structural assignment. Isocyanide 5 and synthetic diastereomers 5a and 5c showed activity against Plasmodium falciparum malaria parasites (IC ∼1 μM).
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Sun, 31 Dec 2017, 15:55:42 EST