Department of Medicinal Chemistry

Research Interests

Research in the Altman group will focus on the development of new reagents and catalyst systems for synthetic organic chemistry, and application of these methodologies to the synthesis of medicinally relevant molecules and natural products. We are particularly interested in the development of mild and user-friendly methods for fluorinating organic compounds. We are also interested in developing cascade reactions that can efficiently convert simple starting materials into complex structures, and applying these reactions toward the synthesis of important targets.

Synthesis of Organofluorine Compounds

Fluorinated compounds have important applications in medicinal, agricultural and materials chemistry. The simple replacement of a functional group with an analogous fluorinated substituent can drastically modify various molecular properties, such as oxidative and thermal stability, steric, electronic, solubility, and conformational rigidity. One common fluorine group is the trifluoromethyl group (–CF3)

The introduction of a CF3 group is highly challenging and underdeveloped. Typical preparations of the CF3 moiety involve the use of harsh reagents that (a) significantly limit the scope of functional groups tolerated, (b) require specialized equipment and training to conduct, (c) inhibit the ability to introduce a CF3 group at a convenient or late stage of a synthesis, or (d) to prepare a trifluoromethyl derivative from a compound already in hand. Electrophilic and nucleophilic trifluoromethylation reagents have been developed. However, use of these reagents is limited by the limited scope of functional groups that can be transformed, and by poor selectivity for substrates, which leads to low yields and complex mixtures of trifluoromethylated products. Metal-catalyzed nucleophilic or oxidative trifluoromethylation reactions represent an emerging area in synthetic organic chemistry.

We seek to develop user-friendly and mild reagents and/or new catalyst systems for the installation of perfluoroalkyl groups. This methodology should be useful for medicinal, agrochemical and materials chemists.

Transition Metal-Catalyzed Reactions and Complex Molecule Synthesis

Transition metal-catalyzed cascade reactions are efficient for preparing the cores of complex alkaloid structures. We are interested in developing metal-catalyzed reactions that are capable of selectively forming multiple C–C and C–heteroatom bonds, while controlling the relative and/or absolute configuration of multiple stereocenters in a single reaction. This strategy can quickly build complexity in a molecule from simple starting materials. We intend to exploit our developed cyclization reactions for the synthesis of medicinally relevant natural product targets, and for the synthesis of new chemical entities. Products will be submitted directly for high throughput screening (HTS) against relevant cancer cell lines, and/or be incorporated onto known medicinally relevant scaffolds and submitted for HTS.