RESUMEN
The total synthesis of (-)-swainsonine from 2,3-O-isopropylidene-D-erythrose in 12 steps and an overall yield of 28% is reported. The pivotal transformation in our route to this indolizidine alkaloid is the formation of the pyrrolidine ring and C-8a/8 stereodiad through the diastereoselective, bis-cyclofunctionalization of an γ,δ-unsaturated O-alkyl hydroxamate. This transformation is believed to proceed via the intramolecular capture of an N-acyl-N-alkoxyaziridinium ion generated by the diastereoselective addition of a singlet acylnitrenium ion to the pendant alkene.
Asunto(s)
Alquenos/química , Compuestos de Nitrógeno/química , Swainsonina/síntesis química , Cationes/química , Ciclización , Estructura Molecular , Oxidación-ReducciónRESUMEN
The asymmetric total synthesis of the α-glucosidase inhibitor (+)-castanospermine is reported. The central theme in our approach to this polyhydroxylated alkaloid is the simultaneous generation of the piperidine ring and the C-1/8a erythro stereodiad through the diastereoselective, oxamidation of an unsaturated O-alkyl hydroxamate. This process is believed to proceed sequentially via singlet acylnitrenium and aziridinium ion intermediates.
Asunto(s)
Alcaloides/síntesis química , Inhibidores de Glicósido Hidrolasas , Indolizinas/síntesis química , Alcaloides/química , Alcaloides/farmacología , Catálisis , Ciclización , Indolizinas/química , Indolizinas/farmacología , Iones , Estructura Molecular , EstereoisomerismoRESUMEN
The development of a versatile method for the preparation of five- to eight-membered hydroxy lactams that involves the iodine(III)-mediated oxamidation of unsaturated O-alkyl hydroxamates is described. This transformation, which is believed to proceed through the intermediacy of singlet nitrenium and bicyclic N-acyl-N-alkoxyaziridinium ions, is both stereospecific and highly regioselective in most of the 22 cases examined.
Asunto(s)
Ácidos Hidroxámicos/química , Lactamas/química , Ciclización , Estructura MolecularRESUMEN
The enantioselective total synthesis of the potent alpha-glucosidase inhibitors schulzeine A, B, and C and a revision of the proposed C20' configuration of schulzeine A are reported. The central feature of our convergent route to this family of novel marine natural products is the preparation of the common benzo[a]quinolizidine subunit through a substrate-controlled, diastereoselective Pictet-Spengler cyclocondensation.
Asunto(s)
Inhibidores Enzimáticos/síntesis química , Inhibidores de Glicósido Hidrolasas , Compuestos Heterocíclicos con 3 Anillos/síntesis química , Lactamas/síntesis química , Quinolizidinas/síntesis química , Ésteres del Ácido Sulfúrico/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Compuestos Heterocíclicos con 3 Anillos/química , Compuestos Heterocíclicos con 3 Anillos/farmacología , Lactamas/química , Lactamas/farmacología , Estructura Molecular , Quinolizidinas/química , Quinolizidinas/farmacología , Estereoisomerismo , Ésteres del Ácido Sulfúrico/química , Ésteres del Ácido Sulfúrico/farmacologíaRESUMEN
A synthetic route to the neurotrophic agent (+)-lactacystin has been developed utilizing a base-promoted intramolecular alkylidenecarbene C-H insertion as the key transformation.