Alta-ur-Rahman (Ed.) Studies in Natural Products Chemistry, Vol. 35 © 2008 Elsevier B.V. All rights reserved. NOVEL DOMINO REACTIONS FOR SYNTHESIS OF BIOACTIVE DITERPENOIDS AND ALKALOIDS SHANTA S. BHAR AND M.M.V. RAMANA Department of Chemistry, University of Mumbai, Santacruz(E), Mumbai- 400098, INDIA ABSTRACT: In the synthesis of relevant organic compounds such as natural products and analogues, the proportion of the number of steps coupled with the increase of complexity is now a universal paradigm to ascertain the quality and efficiency of a process. Alongwith providing accessibility to a multitude of diversified classes of natural products such as alkaloids, terpenoids, steroids and others, these criteria have been addressed by us via the application of domino processes. The acid-catalyzed intermolecular cyclization has been used as a viable synthetic tool for the stereospecific formation of different classes of polycyclic natural products. INTRODUCTION The synthesis of bioactive natural products, agrochemicals, pharmaceuticals have evolved to allow the formation of complex molecules in a few steps, starting from simple substrates. Any synthetic procedure involves either linear retrosynthesis or disconnection approach. The linear pathway leads to a consecutive synthesis and the branching pathway leads to a convergent synthesis. In a convergent synthesis, the several pieces of a molecule are synthesized individually and the final target is sequentially assembled from the fragments. In contrast, the consecutive synthesis involves the stepwise formation of the final complex molecule. It is apparent that the convergent synthesis will have fewer consecutive steps in the overall synthesis (Chart-I) . In a synthesis involving fifteen steps, if each step has a mean yield of 90%, the overall yield of final products is (0.9)15 "" 0.21 (21%). If the largest sequence is split and divided into convergent solution, there would be only four consecutive steps in a perfectly convergent pathway. The yield of the final product would be (0.9)4"" 0.66 (66%). It is difficult, however to achieve such a perfect convergence, since functional group manipulation, steric considerations, and asymmetry lead to "imperfections" [I] . An example of a convergent synthesis used by Fuchs[2] for the synthesis of prostaglandin E 2 (PGE 2 ) is illustrated in Chart-2, while an example of consecutive synthesis used by Corey[3] for the synthesis of prostaglandin E 2 (PGE 2 ) is illustrated in Chart-3. 399