ASYMMETRIC CATALYSIS AND SYNTHESIS
Our group has keen interests in asymmetric catalysis/synthesis. Currently, the focus has been placed in developing enantioselective processes that can be promoted by small organic molecules. In particular, we are interested in devising highly efficient and versatile catalytic systems that can be readily derived from the chiral pools, and intend to apply our methodologies for the preparation of biologically important and synthetically useful molecules.
Amino catalysis promoted by primary amino acids/amines
L-Proline and its analogues have been predominantly used in amino catalysis. We initiated a research program in which primary amino acids/amines, rather than the secondary pyrrolidine moiety, were utilized as the catalyst for a range of important asymmetric transformations. We demonstrated that primary amine organic catalysts have often shown to be complementary or superior, in comparison with secondary amine-mediated processes. For instance, we discovered that natural tryptophan and silylated threonine were efficient catalysts for the direct aldol and Mannich reaction in aqueous media, respectively.
Amino acid-derived novel tertiary amine-thiourea bifunctional catalysts
Amino acids are probably the most readily available, most versatile and most economical chiral building blocks available to chemists, therefore, we were intrigued by the possibility of deriving a wide array of novel bi(multi)functional organocatalysts from simple amino acid structural scaffolds. To test our hypothesis, we designed tryptophan-based bifunctional thiourea catalysts and applied such catalysts to asymmetric Mannich reaction of fluorinated ketoesters. More recently, this concept has been extended, and more catalysts of this nature and more enantioselective reactions have been developed.
Novel amino acid-incorporating multifunctional catalysts
By incorporating amino acid residues into the existing bifunctional catalyst scaffolds, we derivatized novel multifunctional catalysts, and their effectiveness has been demonstrated in the enantioselective conjugate addition of oxindoles to a vinyl sulfone. We have recently shown wide applications of such catalysts in a number of enantioselective transformations.
Novel bifunctional phosphines derived from amino acids/peptides
Very recently, we questioned the possibility of deriving novel chiral phosphines from amino acids/peptides, and in this context, we have developed a number of bifunctional phosphines that can be readily derived from natural amino acids and peptides. Our catalytic systems have been applied to enantioselective (aza)-Morita-Baylis-Hillman reactions, [3+2] cycloadditions, [4+2] cycloadditions, and allylic alkylations, among others. Our catalysts have the following features:
(i) high structural diversity;
(ii) easy functional tunability;
(iii) good practical stability;
(iv) scalable
Upon strategic applications, these catalysts are extremely powerful in promoting various asymmetric catalytic reactions, and the enantiomeric excesses are mostly above 95%. Our collection of bifunctional chiral phosphine catalysts listed below are currently available at Daicel Chiral Technologies (China) CO.
MEDICINAL CHEMISTRY
Organic chemistry has played a central role in pharmaceutical industry and drug discovery. We are exploring certain therapeutic areas by approaches combining organic synthesis, structure-based drug design and computational chemistry. Specifically, we are interested in the development of novel opioid peptides/opiates, and potentially useful anti-cancer agents.