A multi-substrate screening approach for the identification of a broadly applicable Diels-Alder catalyst.

When developing a synthetic methodology, chemists generally optimize a single substrate and then explore the substrate scope of their method. This approach has led to innumerable and widely-used chemical reactions. However, it frequently provides methods that only work on model substrate-like compounds.

Approaching sub-ppm-level asymmetric organocatalysis of a highly challenging and scalable carbon-carbon bond forming reaction.

The chemical synthesis of organic molecules involves, at its very essence, the creation of carbon-carbon bonds. In this context, the aldol reaction is among the most important synthetic methods, and a wide variety of catalytic and stereoselective versions have been reported. However, aldolizations yielding tertiary aldols, which result from the reaction of an enolate with a ketone, are challenging and only a few catalytic asymmetric Mukaiyama aldol reactions with ketones as electrophiles have been described.

Synthesis and Topoisomerase I inhibitory properties of klavuzon derivatives.

Klavuzon is a naphthalen-1-yl substituted α,β-unsaturated δ-lactone derivative, and is one of the anti-proliferative members of this class of compounds. Asymmetric and racemic syntheses of novel α,β-unsaturated δ-lactone derivatives are important to investigate their potential for the treatment of cancer. In this study, asymmetric and racemic syntheses of heteroatom-substituted klavuzon derivatives are reported.

Synthesis of 5'-O-DMT-2'-O-TBS Mononucleosides Using an Organic Catalyst.

This unit describes a highly effective method to produce 5'-O-DMT-2'-O-TBS mononucleosides selectively using a small organic catalyst. This methodology avoids the tedious protection/deprotection strategy necessary to differentiate the 2'- and 3'-hydroxyl groups in a ribonucleoside. The catalyst was synthesized in two steps, starting from the condensation of valinol and cyclopentyl aldehyde, followed by anionic addition of N-methylimidazole.

Practical silyl protection of ribonucleosides.

Herein we report the site-selective silylation of the ribonucelosides. The method enables a simple and efficient procedure for accessing suitably protected monomers for automated RNA synthesis. Switching to the opposite enantiomer of the catalyst allows for the selective silylation of the 3'-hydroxyl, which could be used in the synthesis of unnatural RNA or for the analoging of ribonucelosides.

Continuous flow, highly enantioselective Michael additions catalyzed by a PS-supported squaramide.

A polystyrene (PS) supported bifunctional squaramide organocatalyst promotes fast Michael addition of 2-hydroxy-1,4-naphthoquinone to nitroalkenes with very high enantioselectivities at low catalyst loadings. The polystyrene supported catalyst can be recycled up to 10 times without any decrease in enantioselectivity (average 96% ee) and adapted to continuous flow operation (24 h). A single flow experiment involving six different nitroalkenes in a sequential manner highlights the applicability of this methodology for rapid access to chemical diversity.

Polystyrene-supported diarylprolinol ethers as highly efficient organocatalysts for Michael-type reactions.

α,α-Diphenylprolinol methyl- and trimethylsilyl ethers anchored onto a polystyrene resin have been prepared by a copper-catalyzed azide-alkyne cycloadditions (CuAAC). The catalytic activity and enantioselectivity displayed by the O-trimethylsilyl derivative are comparable to those exhibited by the best known homogeneous catalysts for the addition of aldehydes to nitroolefins and of malonates or nitromethane to α,β-unsaturated aldehydes. The combination of the catalytic unit, the triazole linker, and the polymeric matrix provides unprecedented substrate selectivity, in favor of linear, short-chain aldehydes, when the organocatalyzed reaction proceeds by an enamine mechanism.

Michael acceptor properties of 6-bicycloaryl substituted (R)-5,6-dihydro-2H-pyran-2-ones.

The mechanism of action for alpha,beta-unsaturated lactones can be explained by their Michael acceptor properties. They have the potential of being covalently binding inhibitors by accepting nucleophiles from target proteins. In this work, Michael addition reactions of ethanethiol with 6-bicycloaryl substituted 5,6-dihydro-2H-pyran-2-ones were studied to explore the existence of such interactions.

6-Bicycloaryl substituted (S)- and (R)-5,6-dihydro-2H-pyran-2-ones: asymmetric synthesis, and anti-proliferative properties.

(R)-Goniothalamin, is a member of styryl lactones, possesses selective cytotoxicity against cancer cell lines. In this work, replacement of styryl substituent with 2-naphthyl and 3-quinoyl gave new analogues which may have less conformational changes compared to the lead compound. Anti-proliferative tests indicated that 2-naphthyl substituted (R)-5,6-dihydro-2H-pyran-2-one has slightly better cytotoxicity than (R)-goniothalamin.