Combination of microwave reactions with fluorous separations in the palladium-catalyzed synthesis of aryl sulfides.
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Coupling of microwave reactions with fluorous separations can dramatically increase the efficiency of high-speed synthesis. Described in this paper is a fluorous synthesis of aryl sulfides by palladium-catalyzed cross-coupling of aryl perfluoroalkylsulfonates (C8F17O2SOAr) with thiols (RSH) under microwave irradiation. Fluorous solid-phase extractions (F-SPE) are employed for the purification of reaction mixtures. No fluorous solvents are involved in reaction and separation processes. The fluorous synthesis is further extended to the multi-step synthesis of substituted hydantoin and amide scaffolds. (+info)
Asymmetric catalysis: an enabling science.
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Chirality of organic molecules plays an enormous role in areas ranging from medicine to material science, yet the synthesis of such entities in one enantiomeric form is one of the most difficult challenges. The advances being made stem from the convergence of a broader understanding of theory and how structure begets function, the developments in the interface between organic and inorganic chemistry and, most notably, the organic chemistry of the transition metals, and the continuing advancements in the tools to help define structure, especially in solution. General themes for designing catalysts to effect asymmetric induction are helping to make this strategy more useful, in general, with the resultant effect of a marked enhancement of synthetic efficiency. (+info)
Asymmetric catalysis in complex target synthesis.
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This article describes three distinct strategies by which stereochemically complex molecules are synthesized and the ways asymmetric catalysis can impact on all three. The development of general methods to prepare synthetically useful building blocks leads to an expanded "chiral pool" of potential starting materials for asymmetric synthesis. The possibility of discovering new reactions to access new types of building blocks is particularly attractive and serves to help define the frontiers of the field. Asymmetric catalysis can also be applied to diastereoselective synthesis such that the stereochemistry of the catalyst, and not that of the substrate, determines the relative configuration of the product. Finally, in reactions where multiple stereocenters are generated simultaneously or in tandem, catalyst and substrate control can operate in a complementary manner to achieve one of many possible stereochemical outcomes selectively. (+info)
Stuart Schreiber.
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Stuart Schreiber is an Investigator at the Howard Hughes Medical Institute and Morris Loeb Professor in the Department of Chemistry and Chemical Biology at Harvard University. His chemical biology research, which uses small molecules derived from diversity-oriented synthesis, observational screens and information science, has uncovered principles that underlie information transfer and storage in cells. Harvard's ICCB and its affiliated, NCI-sponsored Initiative for Chemical Genetics and the NIGMS-sponsored Center of Excellence in Chemical Methodologies and Library Development are facilitating his research. (+info)
A structure-activity relationship study was performed on cyclic RGD peptides using a combination of multisubstituted alkene dipeptide isosteres. To clarify the effects on bioactivity of a valine N-methyl group in the cyclo(-Arg-Gly-Asp-D-Phe-MeVal-) peptide developed by Kessler's group, novel D-Phe-Val-type isosteres with methyl-substituting groups on the olefin were designed and synthesized. Syntheses of D-Phe-psi[(E)-CH=CMe]-Val-type isosteres were carried out in essentially identical fashion to the previously reported preparation of psi[(E)-CH=CH]-type congeners. Alternatively, D-Phe-psi[(E)-CMe=CX]-Val-type isosteres (X=H or Me) were synthesized via stereoselective alkylation of beta-(1,3-oxazolidin-2-on-5-yl)-alpha,beta-enoates using organocopper reagents. The resulting four isosteres were utilized in either solution- or solid-phase peptide synthesis to afford the cyclic RGD peptidomimetics, cyclo(-Arg-Gly-Asp-D-Phe-psi[(E)-CX=CX]-Val-) (X=H or Me). alpha(V)beta(3) and alpha(IIb)beta(3) integrin antagonistic activities of the peptidomimetics along with Kessler's peptides were comparatively evaluated. In addition, structural calculations of these compounds by simulated annealing/energy minimization using dihedral and distance restraints derived from (1)H-NMR data in DMSO gave insight into the effects of the valine N-methyl group as well as the D-phenylalanine carbonyl oxygen. (+info)
Oligomeric catechins: an enabling synthetic strategy by orthogonal activation and C(8) protection.
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Controlled formation of oligomeric catechins has become possible by an orthogonal synthetic strategy. Bromo-capping of the C(8) position of the flavan skeleton enabled the equimolar coupling of electrophilic and nucleophilic catechin derivatives, enabling an efficient synthetic strategy to complex catechin oligomers. (+info)
Synthetic studies of roquefortine C: synthesis of isoroquefortine C and a heterocycle.
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The syntheses of isoroquefortine C and a related heterocycle were achieved by implementation of both intra- and intermolecular vinyl amidation reactions. These accomplishments represent a significant advance in the use of these strategies in the generation of complex molecules. (+info)
Stereocontrolled total synthesis of (+)-vincristine.
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An efficient total synthesis of (+)-vincristine has been accomplished through a stereoselective coupling of demethylvindoline and the eleven-membered carbomethoxyverbanamine presursor. Demethylvindoline was prepared by oxidation of 17-hydroxy-11-methoxytabersonine, followed by regioselective acetylation with mixed anhydride method. Although an initial attempt of coupling by using demethylvindoline formamide was not successful and resulted in recovery of the starting compounds, the reaction using demethylvindoline took place smoothly to furnish the desired bisindole product with the correct stereochemistry at C18'. After formation of the piperidine ring by sequential removal of the protective groups and intramolecular nucleophilic cyclization, the total synthesis of vincristine was completed by formylation of N1. (+info)