A catalytic enantioselective method
for the synthesis of α-quaternary
Mannich-type products is reported. The two-step sequence of (1) Mannich
reaction followed by (2) decarboxylative enantioselective allylic
alkylation serves as a novel strategy to in effect access asymmetric
Mannich-type products of “thermodynamic” enolates of
substrates possessing additional enolizable positions and acidic protons.
Palladium-catalyzed decarboxylative allylic alkylation enables the
enantioselective synthesis of five-, six-, and seven-membered ketone,
lactam, and other heterocyclic systems. The mild reaction conditions
are notable given the acidic free N–H groups and high functional
group tolerance in each of the substrates. The utility of this method
is highlighted in the first total synthesis of (+)-sibirinine.
The one-electron reduction of [Pd3(C7H7)2(CH3CN)3][BF4]2 in acetonitrile resulted in the formation of the dimer dication [Pd6(C7H7)4(CH3CN)4][BF4]2, whose structure containing a novel bitriangle hexapalladium skeleton was determined by X-ray crystallographic analysis. The dimer is stable in CD3CN at ambient temperature for several days but is highly air-sensitive. Similarly, the cycloheptatriene tripalladium complex [Pd3(C7H7R)2(CH3CN)3][BF4]2 (R = H, t-Bu) dimerized upon one-electron reduction. Both monomer and dimer of cycloheptatriene complexes were structurally determined by X-ray crystallographic analyses.
Six in one blow: Total syntheses of all the amathaspiramide alkaloids have been accomplished. Rapid construction of the diazaspiro[3.3]nonane core combined with regio‐ and diastereoselective reduction of the cyclic imide moiety with DIBAL established the route to the common structural motif. The late‐stage reduction of the lactam to an imine functionality mediated by Schwartz's reagent was the key to the streamlined syntheses.
Assisted by the total syntheses of all the amathaspiramides, six natural products and four synthetic intermediates with partially fluctuating structures were prepared and subjected to a growth inhibition assay in four human cancer cell lines. The results showed amathaspiramides A, C, and E had moderate antiproliferative activity. Examination of the structure-activity relationship revealed the importance of the amine or imine substructure on the pyrrolidine moiety and the 8R stereochemistry on the N-acyl hemiaminal moiety for the antiproliferative activity of amathaspiramide alkaloids.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.