The Nakada Group

Total synthesis of bioactive natural products, development of new reactions and methodologies directed at the total synthesis, and investigation of chemical biology on the basis of the total synthesis are the major projects currently underway in Nakada's laboratory.

1. Research on Total Synthesis of Bioactive Natural Products

Natural Products Synthesized in Nakada's Lab

Natural Product Synthesis in Progres

2. Research on New Reaction and Methodology

2-1. Asymmetric Catalysis of Nozaki-Hiyama Reactions

Asymmetric catalysis of Nozaki-Hiyama reactions has been successfully carried out using the new chiral tridentate ligand.

2-1-1. Catalytic Asymmetric Nozaki-Hiyama Allylation and Methallylation

Applicable to a wide range of aldehydes.

A chromium-ligand complex isrecyclable and stable in air.

The reaction can be carried out by sequential addition of the ligand and reagents.

2-1-2. Catalytic Asymmetric Nozaki-Hiyama Propargylation

Propargylation occurs without the formation of allenic alcohol.

2-1-3. Catalytic Asymmetric Nozaki-Hiyama Allenylation

First example of catalytic asymmetric Nozaki-Hiyama allenylation. DMS is used as surrogate hydrogen.

2-2. Catalytic Asymmetric Intramolecular Cyclopropanation (CAIMCP)

Highly crystalline products with high enantiomeric excess are prepared in high yield.

Applicable to a wide range of α-diazo-β-keto sulfones.

2-3. Preparation of Chiral Building Blocks with Biocatalyst

Baker's-yeast-mediated reduction of cycloalkane-1,3-diones with a methyl group and a protected hydroxymethyl group provides the corresponding hydroxyketone with high diastereo- and enantioselectivity.

Diethyl 2-methyl-2-phenylmalonate and diethyl 2-cinnamyl-2-methylmalonate are converted into corresponding mono-esters with high yield and enantioselectivity.

3. Research on chemical biology

3-1. Design and synthesis of new MK8383 analogs and antifungal reagents

MK8383 has promising antifungal activity and is expected to be an effective fungicide. However, it is very sensitive to light. A new MK8383 derivative, which was designed and synthesized on the basis of the first total syntheses of (+)-phomopsidin and MK8383, showed excellent light stability in addition to having promising antifungal activity.