About us

Professor
Dr. Tomohiko OHWADA, Ph. D., Organic and Medicinal Chemistry
Assistant Professor
Dr. Yuko OTANI, Ph. D., Synthesis of Molecular Architectures, Computational Chemistry

Address:

Graduate School of Pharmaceutical Sciences
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
JAPAN

Contact us
Correspondance to:
E-mail:　 yakkagak (at) mol.f.u-tokyo.ac.jp
Dr. Tomohiko Ohwada: ohwada (at) mol.f.u-tokyo.ac.jp

About our research interests:

Aims of Researchs in Our Laboratory: We aims integration of molecular structures and functions/properties which are relevant to biological actions and chemical reactivities. We emphasized on design and synthesis of structurally novel organic molecules which are characteristic in terms of structure (bond) features and intrinsic functions such as chemical reactivities and biological functions.

Research Topics:

1.New Approach to Functionalizing Aromatic Compounds Based on Designed Superelectrophiles: Aromatic structures provide basic architecture for developing functionalized materials such as medicines. However, tools for chemoselective, regioselective and stereoselective introduction of various functional groups onto aromatic rings are still limited in their applicability. This project aims to provide a novel approach to functionalizing aromatic compounds by means of development of the chemistry of newly designed superelectrophiles (dications).
The following example of our reaction represented an oxyfuctionalization of aromatic ring by using an oxygen atom of a nitro group:

2. Synthesis of New Compounds Exhibiting Characteristic Structural Features:
Creation of Stable Helical Molecules Based on N-pyramidal Amide We revealed and utilize the structural features of N-substituted 7-azabicyclo[2.2.1]heptane derivatives which induce N-pyramidalization of amides, sufonamides and nitrosamines and other related functional groups.
We showed that amides of bicyclic 7-azabicyclo[2.2.1]heptane are intrinsically nitrogen-pyramidal. Single-crystal X-ray diffraction structures of some relevant bicyclic amides, including the prototype N-benzoyl-7-azabicyclo[2.2.1]heptane, exhibited nitrogen-pyramidalization in the solid state. We also evaluated the rotational barriers about the amide bonds of various N-benzoyl-7-azabicyclo[2.2.1]heptanes in solution.
The observed reduction of the rotational barriers of the bicyclic amides, as compared with those of the monocyclic pyrrolidine amides, is consistent with a nitrogen-pyramidal structure of 7-azabicyclo[2.2.1]heptane amides in solution.

Scheme 2 Intrinsic Feature of Nitrogen-pyramidalization of Amides of 7-bicyclo[2.2.1]heptanes

Transnitosation of N-Pyramidal Nitrosamines to Thiol N-Nitrosamines can be considered as potential NO/NO+ donors. We showed that aliphatic N-nitrosoamines of 7-azabicyclo[2.2.1]heptanes could undergo heterolytic N-NO bond cleavage. Based on the observation of reduced rotational barriers of the N-NO bonds in solution and nitrogen-pyramidal structures of the N-nitroso group in the solid state, we postulate that N-NO bond cleavage of N-nitrosamines is enhanced by a reduction of the resonance in the N-NO group. The N-NO bond of the N-nitroso derivatives of 7-azabicyclo[2.2.1]heptanes tends to be weak. We described the S-transnitrosation reaction of aliphatic N-nitroso derivatives of 7-azabicyclo[2.2.1]heptanes, which resemble conformationally constrained proline derivatives, and its chemical features, i.e., reactivity and chemoselectivity. These N-nitroso derivatives of 7-azabicyclo[2.2.1]heptanes do not act as NO donors themselves, but can transnitrosate thiols.

Scheme 3 Transnitrosation of N-pyramidal Nitrosamines to Thiols

3. Design and synthesis of intelligent molecules: Chemical modulators relevant to biological phenomena around membranes: 1) Design and synthesis of K+ ion channel modulators, and 2) phospholipid-like modulators.


Scheme 4 Our 1st Generation of BK channel openers

4. Computational Studies of Organic Reactions, Structural Basis and Drug Design. Application of ab initio molecular orbital calculations in a part of efforts to understand the structural features, selectivities, and reaction mechanisms. Computer-assisted design of the molecules. A combination of computational works with experimental observations is encouraged.