Catalyst-Controlled Stereoselective Synthesis Secures the Structure of the Antimalarial Isocyanoterpene Pustulosaisonitrile-1.
J Org Chem
; 82(24): 13313-13323, 2017 12 15.
Article
en En
| MEDLINE
| ID: mdl-29124922
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 (IC50 â¼1 µM).
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
/
Triazinas
/
Antimaláricos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2017
Tipo del documento:
Article