Our group at IIT-Bombay has been engaged in developing new and novel synthetic methods for the preparation of unusual a-amino acids (AAAs) and polycyclic compounds. Synthetic AAAs have been found to play a significant role in the interface of chemistry and biology. Our approach to these AAAs is based on the development of new building blocks embodying AAA moiety, which are useful in the preparation of diverse AAAs of higher order ring systems.

Recently, we have demonstrated that solid-liquid phase-transfer catalysis is remarkably effective in the preparation of constrained AAAs with highly electron deficient and electron-rich side chains using ethyl isocyanoacetate as a glycine equivalent. This approach has been successfully applied for the synthesis of several indane-based AAAs, which are inaccessible, by the other known methods. This methodology is also extended to indane-based constrained a-amino acid derivatives containing crown-ether side chain for the first time. Parallel to this methodology, we have shown that 2+2+2 and 4+2 cycloaddition reactions are useful for the synthesis of constrained analogues of phenylalanine. Using 2+2+2 cycloaddition reaction we have prepared the indane based amino acids. Our cycloaddition methodology demonstrates the feasibility of introducing diverse functionalities by judicious choice of the reacting partners. Post-translational peptide modification was also established via 2+2+2 cycloaddition reaction. In connection with various unusual AAA derivatives we have utilized ring-closing metathesis, enyne metathesis, and cross metathesis reactions as key steps.

In connection with our interest to prepare exotic non-natural products such as dodecahedron, our group has developed a simple and straight forward three-step methodology for cyclopentane annulation using inexpensive reagents. By this method, various hexaquinane ring systems were prepared from the readily available bicyclo[3.3.0]octane dione derivatives. A new method for spiro-cyclopentane annulation was demonstrated using ring-closing metathesis reaction as a key step. Fragmentation methodology was utilized to allylate some polycyclic diketones where ionic conditions are inappropriate. We have prepared various star-shaped thiophene derivatives using tetrachlorosilane mediated trimerization and Suzuki coupling reactions as key steps. This methodology has been extended to various dendrimer-type molecules.