Synthesis Of Natural Products Based On Cyclohexadienes

Abstract

The thesis entitled "Synthesis of Natural Products Based on Cyclohexadienes" consists of two chapters. Chapter 1 is divided into two parts. Part I gives a brief introduction to the structure, synthesis, biosynthesis and biological activities of some naturally occurring phthalides (eg. mycophenolic acid 1, zinniol2, phthalides 3 & 4). A general strategy for the preparation of highly substituted phthalides is also described. Cycloaddition of 1,s-dimethoxycoclohexa-1, 4-diene with dimethylacetylenedicarboxylate(DMAD) followed by an Alder-Rickert reaction gave the diester 5 which upon hydrolysis with KOH and refluxing with acetic anhydride gave the phthalic anhydride 6. Regioselective reductions of the anhydride 6 gave the phthalides 7 and 8. Using a similar strategy the phthalides 11 & 12 were prepared from 2,6dimethoxytoluene through the intermediates 9 & 10. The aromatic ethers 13 & 14 upon Birch reduction followed by Diels-Alder reaction with maleic anhydride gave the bicyclic anhydrides 15 & 16 respectively. Attempts to dehydrogenate 15 using variety of conditions failed. But refluxing 15 in nitrobenzene gave a poor yield of 17 which is an important intermediate in the synthesis of mycophenolic acid. Part II describes the first total synthesis of zinniol 2, phthalide-1 3 & phthalide-2 4. Thus the diene 18, obtained from 2-methylcyclohexane-1,3dione, upon Diels-Alder and Alder-Rickert with DMAD gave the diester 19. Prenylation of 19 afforded the diester 20 which was convened into 21 upon hydrolysis and DCC treatment. DIBAL reduction of 20 gave Zinniol 2 which on oxidation provided the phthalides 3 & 4 (7:3 ratio respectively). The anhydride 21, on selective reduction, gave the same phthalides in 2:8 ratio which could be readily separated and characterized.