Hydroazulenic lactone

The complex structure along with the potential medicinal properties of the naturally occuring hydroazulenic lactones have stimula-ted an intensive synthetic activity in the field. 

A rather different approach to the hydroazulenic synthesis has been adopted by Hendrickson and Boeckman. Treatment of 1-cyclopentenylcarboxalde-hyde (411) with the pyrrolidine enamine of cyclopentanone (412) yielded the thermodynamically most stable adduct (413) which, on quaternization and base-induced fragmentation, gave the acid (414) in 25% yield. Furthermore, the acid (414) has been converted into the epoxide (415) and the (5-lactone (416), both of which are potential synthetic precursors of guaiane-type sesquiterpenoids, e.g. pseudoguaianolides. 

In connection with a synthesis of the hydroazulenic sesquiterpene kessanol (304), Knoevenagel condensation of photocitral-A (302) with ethyl cyanoacetate was found to give (303) as a single isomer. The following sequence includes an intramolecular Prins reaction initiated with SnCU. In Isobe s synthesis of vemolepin (307) the two carbons of the -y-iactone are introduced by a Knoevenagei condensation. Reaction of ketone (305) with di-f-butyl maionate followed by treatment with DBU affords (306), which is transformed to the a,a -dihydroxy compound (308). Hydrolysis of the esters foliowed by decarboxy-iation, formation of the y-lactone, Mannich reaction and elimination yields vemolepin (307 Scheme 58).3"... 

Among the many isolated sesquiterpene lactones, the nonisoprenoid hydroazulenic pseudogua-ianolides are the largest family51. Most of these tricyclic compounds contain a c -fused /3-lactone subunit, as well as a trans-fused hydroazulene. In a synthesis of damsin. a./i-unsatu-rated lactone 5 was hydrogenated over platinum on carbon to yield an 85 15 mixture of the C-6-isomeric products 6 with a <7s-fused lactone subunit49. 

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