ABSTRACT
A method is described for the joining of two α-lithiated C(sp3) stereocenters efficiently and with retention of configuration. The key step involves the effective removal of two electrons from a chiral organocuprate R2CuLi, by i-propyl 2,4-dinitrobenzoate to form a Cu(III) complex that undergoes at -90 °C accelerated reductive elimination enantioselectively and exclusively without the formation of free radicals.
ABSTRACT
The coordination of chiral ligands to Lewis acid metal derivatives, a useful strategy for enantioselective, electrophilic catalysis, generally leads to a lower level of catalytic activity than that of the original uncomplexed compound. Activation by further attachment of a proton or strong Lewis acid to the complex provides a way to overcome the deactivating effect of a chiral ligand. The research described herein has demonstrated that further enhancement of catalytic activity is possible by the judicious placement of fluorine substituents in the chiral ligand. This approach has led to a new, second-generation family of chiral oxazaborolidinium cationic species which can be used to effect many Diels-Alder reactions in >95% yield and >95% ee using catalyst loadings at the 1-2 mol % level. The easy recovery of the chiral ligand makes the application of these new catalysts especially attractive for large-scale synthesis.
ABSTRACT
A number of diseases can result from abnormal gene expression. One of the approaches for treating such diseases is gene therapy to inhibit expression of a particular gene in a specific cell population by RNA interference. Use of efficient delivery vehicles increases the safety and success of gene therapy. Here we report the development of functionalized biocompatible fluorescent nanoparticles from para amino benzoic acid nanoparticles for efficient delivery of short interfering RNA (siRNA). These nanoparticles were non-toxic and did not interfere with progression of the cell cycle. The intrinsic fluorescent nature of these nanoparticles allows easy tracking and an opportunity for diagnostic applications. Human Bcl-2 siRNA was complexed with these nanoparticles to inhibit expression in cells at both the transcriptional and translational levels. Our findings indicated high gene transfection efficiency. These biocompatible nanoparticles allow targeted delivery of siRNA, providing an efficient vehicle for gene delivery.
Subject(s)
Benzoates/chemistry , Biocompatible Materials/administration & dosage , Drug Delivery Systems , Nanoparticles/administration & dosage , Neoplasms/drug therapy , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , RNA, Small Interfering/administration & dosage , Apoptosis , Biocompatible Materials/chemistry , Blotting, Western , Cell Cycle , Cell Proliferation , Endocytosis , Flow Cytometry , Gene Silencing , Genetic Therapy , HeLa Cells , Humans , Immunoenzyme Techniques , Nanoparticles/chemistry , Neoplasms/pathology , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
A concise and highly stereoselective total synthesis of manzacidin B and its congeners has been developed following chelation-controlled syn-epoxidation and Lewis acid catalyzed intramolecular regioselective epoxide ring opening to generate the quarternary amine center. Elaboration of the triol moiety to the target molecule was achieved in good overall yield, representing practical total syntheses of manzacidin B and its congeners. From the XRD, NMR, and analytical data, the correct structure of natural manzacidin B, (4R,5R,6R)-6, was confirmed.
Subject(s)
Pyrimidines/chemical synthesis , Pyrroles/chemical synthesis , Amines/chemistry , Catalysis , Epoxy Compounds/chemistry , Models, Molecular , Molecular Structure , StereoisomerismABSTRACT
Highly stereoselective total syntheses of polyrhacitide A and epi-cryptocaryolone have been achieved in 11 steps with high overall yield of 24% and 28%, respectively, following a recently developed strategy for the construction of trans-2,6-disubstituted-3,4-dihydropyrans. In this report, the versatility of iodo-cyclization for the total syntheses of polyrhacitide A and epi-cryptocaryolone is demonstrated.
