RESUMEN
An asymmetric total synthesis of the guaiane sesquiterpene (-)-englerin A, a potent and selective inhibitor of the growth of renal cancer cell lines, was accomplished. The basis of the approach is a highly diastereo- and enantioselective carbonyl ylide cycloaddition with an ethyl vinyl ether dipolarophile under catalysis by dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], [Rh2 (S-TCPTTL)4 ], to construct the oxabicyclo[3.2.1]octane framework with concomitant introduction of the oxygen substituent at C9 on the exo-face. Another notable feature of the synthesis is ruthenium tetraoxide-catalyzed chemoselective oxidative conversion of C9 ethyl ether to C9 acetate.
Asunto(s)
Antineoplásicos/síntesis química , Complejos de Coordinación/química , Éteres de Etila/química , Neoplasias Renales/química , Sesquiterpenos de Guayano/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Factores Biológicos/química , Catálisis , Línea Celular Tumoral , Reacción de Cicloadición , Humanos , Neoplasias Renales/patología , Estructura Molecular , Rodio/química , Sesquiterpenos de Guayano/química , EstereoisomerismoRESUMEN
The reaction of a six-membered cyclic formyl-carbonyl ylide derived from alpha-diazo-beta-ketoester with phenylacetylene derivatives under the catalysis of dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], Rh(2)(S-TCPTTL)(4), provides cycloadducts containing an 8-oxabicyclo[3.2.1]octane ring system in up to 97% ee. This represents the first example of an enantioselective 1,3-dipolar cycloaddition of a cyclic formyl-carbonyl ylide. Using this catalytic process, an asymmetric synthesis of endo-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one natural product 1 from Ligusticum chuanxing Hort. has been achieved.
Asunto(s)
Factores Biológicos/síntesis química , Compuestos Bicíclicos con Puentes/química , Cetonas/química , Ligusticum/química , Compuestos Organometálicos/química , Rodio/química , Factores Biológicos/química , Catálisis , Ciclización , Estructura Molecular , EstereoisomerismoRESUMEN
The first total synthesis of brasilicardins A and C, novel diterpenoid-saccharide-amino acid hybrid metabolites with unique immunosuppressive activity, is described. The key step is a Diels-Alder/reductive angular methylation sequence capitalizing on a trans-fused bicyclic α-cyano-α,ß-enone as its precursor to construct the 8,10-dimethyl-trans/syn/trans-perhydrophenanthrene skeleton. Other notable features include an anti-selective aldol reaction, a stereocontrolled glycosylation of a C2 alcohol, and a one-pot, two-step global deprotection sequence that did not damage these sensitive molecules.