RESUMO
Syntheses of two natural products derived from the ent-kaurene kaurenoic acid are described for the first time using regio- and diastereoselective oxidations. Palladium- and manganese-mediated oxidations were used to accomplish the syntheses of two ent-beyerane metabolites. The use of the White-Gormisky-Zhao catalyst Mn(CF3-PDP) enabled the first application of a nondirected metal-catalyzed oxidation in an unactivated C-H bond in a total synthesis.
Assuntos
Diterpenos do Tipo Caurano , Diterpenos do Tipo Caurano/química , OxirreduçãoRESUMO
In this communication, the enantioselective synthesis of phthalides and isochromanones is described through a new palladium-catalyzed Heck-Matsuda arylation/NaBH4 -reduction/lactonization sequence of 2,3- and 2,5-dihydrofurans in good overall yields and excellent enantioselectivities (up to 98:2 er). This expeditious synthesis of chiral Heck lactol intermediates allowed the diversification of the strategy to obtain medicinally relevant chiral lactones, amines, and olefins. The natural product 3-butylphthalide was obtained in three steps with an overall yield of 33 % yield in 98:2 er.
RESUMO
The first total synthesis of (-)-marinisporolide C is described, which establishes unequivocally the relative and absolute configuration of this oxopolyene macrolide. Key features of this synthesis include a series of highly stereoselective aldol reactions followed by directed reductions to build the polyol domain, a Stille cross-coupling reaction to assemble the polyene, and an intramolecular Horner-Wadsworth-Emmons olefination to forge the macrocyclic ring. Despite the initial approach to marinisporolide A using a Yamaguchi macrolactonization reaction that was unsuccessful due to steric hindrance of the oxygen at the C33 position, we were able to prepare a known derivative of marinisporolide A and consequently confirm its stereochemical assignment.
Assuntos
Macrolídeos/síntese química , Macrolídeos/química , Estrutura Molecular , EstereoisomerismoRESUMO
The first total synthesis of (-)-marinisporolide C was performed in 25 steps (longest linear sequence) and an overall yield of 1%. Due to the high degree of convergence and robustness, the C9-C35 fragment that corresponds to the polyol portion was obtained in gram quantity. Highlights of this synthesis include five highly stereoselective aldol reactions responsible for the construction of five C-C bonds and six stereogenic centers. Additionally, a very efficient Julia-Kocienski reaction was used to install a C22-C23 double bond, and the macrocyclic ring was closed using an intramolecular Horner-Wadsworth-Emmons olefination.
Assuntos
Macrolídeos/síntese química , Actinobacteria/química , Aldeídos/química , Macrolídeos/química , Biologia Marinha , Estrutura Molecular , EstereoisomerismoRESUMO
In this work, we show the influence of the volume of the ß-substituents on the levels of 1,5-stereoselectivities of aldol reactions of boron enolates generated from ß-alkoxy methylketones with aldehydes. Excellent levels of 1,5-syn stereoinduction were obtained when the ß-protecting group is a silicon ether. This remarkable selectivity is attributed to the volume of the ß-bulky substituent of the corresponding boron enolate. We have investigated a stereochemical model using DFT analysis to rationalize the sense of 1,5-syn stereoselectivities of ß-alkyl-ß-alkoxy methylketones.
RESUMO
Moderate to good levels of substrate-based 1,5-syn-stereocontrol could be achieved in the boron-mediated aldol reactions of ß-tert-butyl methylketones with achiral aldehydes, independent of the nature of the ß-alkoxy protecting group (P = PMB or TBS). The analysis of the relative energies of the transition structures by theoretical calculations using the density functional B3LYP shows relative energies favoring the corresponding OUT-1,5-SYN transition structures, explaining the observed 1,5-syn stereoinduction.