TIFR
Department of Chemical Sciences
School of Natural Sciences

August 10, 2015 at 4.00 pm in AG-69

Title :

Domino Strategies for Syntheses of Natural Products and New Molecular Scaffolds

Abstract :

Domino and multicomponent reactions are always attractive and they are expected to provide the target molecules efficiently in a shortest possible route. Our group has been engaged in designing simple and efficient domino strategies for the syntheses of biologically active natural products and natural product like molecules. In this lecture, our efforts leading to syntheses of vinigrol, cyclic guanidines and N-heterocyclic amides will be discussed in details.

Vinigrol,1 a unique diterpene containing the decahydro-1,5-butanonaphthalene carbon skeleton was shown to exhibit a broad spectrum of biological activity. Besides the multiple sites of oxygenation, vinigrol contains a tricyclic core having a cis-fused [4.4.0] system bridged by an eight-membered ring and eight contiguous stereocenters. We recently reported2 an enantioselective formal synthesis of vinigrol involving a1-2-3 strategy: one pot and 2-reactions with the formation of3-rings leading to the core structure of vinigrol from its stereochemically well-defined acyclic precursor.

The cyclic guanidines3 and N-heterocyclic amides4 are important structural units present in biologically active drug molecules. However, the existing methods suffer from harsh conditions, narrow functional group tolerance, poor atom economy, low yielding and so; it warrants an efficient protocol for their syntheses. We have developed a one-pot Cu-catalyzed cascade routes to these unique cyclic guanidines and N-heterocyclic amides5 from readily available starting materials.

References:

1. Uchida, I.; Ando, T.; Fukami, N.; Yoshida, K.; Hashimoto, M.; Tada, T.; Koda, S.; Morimoto, Y.J. Org. Chem. 1987, 52, 5292–5293.

2. Betkekar, V. V.; Sayyad, A. A.; Kaliappan, K. P.Org. Lett.2014,16, 5540-5543.

3. Subramanian, P.; Kaliappan, K. P. Eur. J. Org. Chem. 2014, 5986–5997.

4. Hou, H.; Wei, Y.; Song, Y.; Mi, L.; Tang, M.; Li, L.; Fan, Y. Angew. Chem. Int. Ed. 2005, 44, 6067-6074.

5. Subramanian, P.; Indu, S.; Kaliappan, K. P. Org. Lett.2014,16, 6212-6215.