New developments in the chemistry of N-acyliminium ions and related intermediates.

Asymmetric organocatalysis in total synthesis – a trial by fire

γ-Amino acids have attracted considerable attention as biologically active compounds in the central nervous system (CNS) of mammals. Over the last few years, significant interest in the stereoselective synthesis and practical application of linear and cyclic chiral γ-amino acids in the synthesis and design of α,β- and β,γ-hybrid peptides with definite secondary structures and design of nanotubes has been reported, thus demonstrating the theoretical interest and the practical importance of γ-amino acids. An overview of synthetic approaches to linear and cyclic chiral γ-amino acids and derivatives is presented. Data on the practical applications of γ-amino acids are also discussed.

Stereoselective synthesis of γ-amino acids

Catalytic asymmetric Michael and Mannich-type reactions of glycine Schiff bases with chiral two-center organocatalysts, tartrate-derived diammonium salts (TaDiASs), are described. On the basis of conformational studies, optimized TaDiASs with a 2,6-disubstituted cyclohexane spiroacetal were newly designed. These TaDiASs catalyzed the asymmetric Michael and Mannich-type reactions of glycine Schiff bases with higher enantioselectivity than previous catalysts. In the Mannich-type reaction, aromatic N-Boc-protected imines (Boc = tert-butoxycarbonyl) as well as enolizable alkyl imines were applicable. As a synthetic application of the catalytic asymmetric Mannich-type reaction with the optimized TaDiASs, we developed a catalytic asymmetric total synthesis of (+)-nemonapride, which is an antipsychotic agent.

Catalytic asymmetric phase-transfer Michael reaction and Mannich-type reaction of glycine Schiff bases with tartrate-derived diammonium salts.

Asymmetric Synthesis of (+)-L-733, 060 and (+)-CP-99, 994 Based on a New Chiral 3-Piperidinol Synthon†

An easy access to protected (4S, 5R)-5-Alkyl-4-hydroxy-2-pyrrolidinones and their use as versatile synthetic intermediates

A versatile approach to the activated form of (3S, 4R)-statine and its analogues

A versatile approach to enantiopure (4S, 5R)-5-alkyl-4-hydroxy-2-pyrrolidinones is described. The key steps involve a regioselective Grignard reagent addition to (S)-malimides, and diastereoselective reductive dehydroxylation of the resulting hemi-azaketals. The flexibility of this methodology has been demonstrated by the synthesis of (2R, 3R)-3-amino-1-benzyl-2-methylpyrrolidine, the parent diamine of antipsychotic agent, emonapride, and the unnatural enantiomer of the β-hydroxy-γ-amino acid residue of hapalosin in lactam form.

An Easy Access to Protected (4S,5R)-5-Alkyl-4-hydroxy-2-pyrrolidinones and Their Use as Versatile Synthetic Intermediates.

A concise and versatile approach to the activated form of (3S, 4R)-statine 6 and its analogues is described. The key steps involve reductive alkylation of (S)-O-tert-butyldimethysilylmalimide 12.

Jing Xing Gao

Papers

An easy access to protected (4S, 5R)-5-Alkyl-4-hydroxy-2-pyrrolidinones and their use as versatile synthetic intermediates

A versatile approach to the activated form of (3S, 4R)-statine and its analogues

An Easy Access to Protected (4S,5R)-5-Alkyl-4-hydroxy-2-pyrrolidinones and Their Use as Versatile Synthetic Intermediates.

A Versatile Approach to the Activated Form of (3S,4R)-Statine and Its Analogues.