Ring-closing metathesis as key step in the synthesis of Luffarin I, 16-epi-Luffarin I and Luffarin A.
Natural sesterterpenolides, luffarin I and luffarin A, from Luffariella geometrica have been synthesized, and this is the first reported synthesis of luffarin A. The Yamaguchi esterification of the nor-diterpenic fragment, obtained from 2.8-15μM, with the appropriate furane alcohols yielded the necessary diene intermediates for the synthesis of the target molecules. The key strategic step in this synthesis was the ring-closing metathesis (RCM) reaction of the diene intermediates. This strategy allowed for the synthesis of 16-epi-luffarin I and analogues for structure-activity relationship (SAR) studies. The most active compound exhibited antiproliferative activity against a panel of six human solid tumour cell lines with [Formula: see text] values in the range 2.8-15 M.
Department of Organic Chemistry, Faculty of Chemistry, University of Salamanca, Salamanca, Spain.
Aitor
A
Urosa
Department of Organic Chemistry, Faculty of Chemistry, University of Salamanca, Salamanca, Spain.
Isidro S
IS
Marcos
Department of Organic Chemistry, Faculty of Chemistry, University of Salamanca, Salamanca, Spain.
David
D
Díez
BioLab, Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), University of La Laguna, La Laguna, Spain.
Gabriela B
GB
Plata
BioLab, Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), University of La Laguna, La Laguna, Spain.
José M
JM
Padrón
Department of Organic Chemistry, Faculty of Chemistry, University of Salamanca, Salamanca, Spain. pbb@usal.es.
Pilar
P
Basabe
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D000067470:Cellular Reprogramming Techniques; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D054830:Sesterterpenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
D054830:Sesterterpenes; C000612888:luffarin A; C000603851:luffarin I; D015107:4-Butyrolactone
Cancer; Faulkner oxidation; Luffarins; Marine natural products; Ring-closing metathesis; Yamaguchi esterefication