Synthetic studies on terpenoids

Abstract

The thesis entitled “Synthetic Studies on Terpenoids” consists of four chapters. Chapter I presents a brief review on the reduction of aromatic substrates with metal-ammonia solutions and applications of the resulting dihydrocompounds to the synthesis of natural products.

Chapter II describes the synthetic efforts towards the sesquiterpene modhephene (1) and attempts towards the construction of a spiro[4,5]decane framework employing a heteroatom-assisted Beckmann fragmentation. The [4.3.3]propellane derivative (2), considered to be an advanced intermediate for modhephene (1), was synthesized by two routes. In the first route, a Beckmann fragmentation of the oxime of the ketone (3), which was obtained by a 5-exo-dig radical cyclization of the acetylenic ketone (4), was employed to obtain the [4.3.3]propellane derivative (2). In the second route, a 5-exo-dig radical cyclization of the acetylenic enone (5) was employed to construct the [4.3.3]propellane derivative (2). The enone (5) was in turn obtained by the Beckmann fragmentation of the oxime of the tricyclic ketone (4).

The synthesis of the spiro[4,5]decane derivative (6) was attempted. It was anticipated that the spiro compound (6) could be obtained by a Beckmann fragmentation of the oxime of the tricyclic ketone (7). The synthesis of the ketone (7) was attempted by an intramolecular alkylation of the keto-tosylate (8). The keto-tosylate (8) was prepared from the alcohol (9), which in turn was obtained from the acid (12) through the intermediates (10) and (11). However, intramolecular alkylation of the keto-tosylate (8) with bases such as LDA and LiHMDS did not result in the desired compound.

Chemical structure diagrams (Structure descriptions would go here.)

The third chapter deals with the construction of the bicyclo[5.3.1]undecane skeleton, present in taxol (13), from tricyclo[5.3.1.0^2,6]undecanes. The tricyclo[5.3.1.0^2,6]undecanone (14) was expected to fragment to the bicyclo[5.3.1]undecane skeleton present in taxol on treatment with acids, analogous to the fragmentation of the bicyclic ketone (16) to the cyclohexenone derivative (17). Similarly, the tricyclic tosylate (18), obtained from the ketone (14), was expected to undergo a Wharton-type fragmentation to the bicyclo[5.3.1]undecane skeleton (19), similar to the fragmentation of the bicyclic tosylate (20) to the cyclohexenone derivative (21). The tricyclo[5.3.1.0^2,6]undecanone (14) was synthesized from the bicyclic alcohol (22), employing a 6-exo-dig radical cyclization as the key step. The bicyclic alcohol (22) was synthesized from the aromatic ether (23), through the intermediate (24). However, all attempts to induce the acid-catalyzed fragmentation of the ketone (14) failed to yield the desired substrate.

Chemical structure diagrams (Structure descriptions would go here.)

The fourth chapter deals with the synthetic studies towards labdane group diterpenes baiyunol (25), calyenone (26), and austrochaprol (27), starting from the naturally occurring diterpene andrographolide (28). The furan (29) was obtained by treatment of the lactone (30) with DMPAL. The lactone (30) was in turn obtained from andrographolide (28) through the intermediate (31). The lactone (31) could be readily transformed into the lactone (32) by isomerization of the exocyclic double bond with PTS, followed by hydrolysis of the resulting diacetate (34). The diol (32) also furnished the furan (33) on treatment with DMPAL. However, the reduction of the tosylate (35) with LAH did not yield the desired compound (36) in good yield