Formal enantioselective synthesis of nhatrangin A.

A new and straightforward synthesis of the C1-C7 core fragment of nhatrangin A was achieved in 14 steps from achiral 3-hydroxybenzaldehyde, without the need of chiral reagents or enzymatic resolution to introduce the chiral centers. The key asymmetric steps include in particular a highly enantioselective organocatalyzed Michael addition on an aryl vinyl ketone, a Sharpless asymmetric epoxidation and a subsequent regioselective ring opening of the resulting chiral epoxide. This work represents the first formal enantioselective synthesis of nhatrangin A.

Solvent-free, metal-free, aza-Prins cyclization: unprecedented access to δ-sultams.

Aza-Prins and the pauper: Aza-Prins cyclization between γ,δ-unsaturated tosylamines and aldehydes was successfully performed under solvent-free and metal-free conditions. When applied to ß,γ-unsaturated sulfonamides, the corresponding δ-sultams were isolated in good yields (see scheme). This approach constitutes a new route to cyclic sulfonamides.

Total synthesis of bistramide†A and its 36(Z)†isomers: differential effect on cell division, differentiation, and apoptosis.

The total synthesis of bistramide A and its 36(Z),39(S) and 36(Z),39(R) isomers shows that these compounds have different effects on cell division and apoptosis. The synthesis relies on a novel enol ether-forming reaction for the spiroketal fragment, a kinetic oxa-Michael cyclization reaction for the tetrahydropyran fragment, and an asymmetric crotonylation reaction for the amino acid fragment. Preliminary biological studies show a distinct pattern of influence of each of the three compounds on cell division, differentiation, and apoptosis in HL-60 cells, thus suggesting that these effects are independent activities of the natural product.

Green chemistry: solvent- and metal-free Prins cyclization. Application to sequential reactions.

Prins cyclization between a homoallylic alcohol and an aldehyde, promoted by trimethylsilyl halide, afforded 4-halo-tetrahydropyrans with good to excellent yields. Thanks to the absence of the solvent and metal, the THP thus obtained have been implicated without purification in several other reactions, in a sequential way, affording in particular new indole derivatives.

The design of novel N-4'-pyridinyl-alpha-methyl proline derivatives as potent catalysts for the kinetic resolution of alcohols.

A novel family of chiral acylation catalysts based on a N-4'-pyridinyl-alpha-methyl proline structure has been studied. A set of 31 compounds has been easily prepared and screened in the kinetic resolution of racemic alcohol 33 resulting in high enantioselectivities in most cases. From results obtained, H-bonding interactions between the catalyst and the substrate would appear essential to afford high enantioselectivity during the catalytic acylation. Additional solvent dependence and anhydride studies have been made to better identify the mechanism. This work has been further extended to the study of a number of structurally different alcohols. Ethanolamine derivatives in particular were found to be highly effective substrates (up to S = 18.8) in the kinetic resolution.