Hydroazulene sesquiterpene

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"... 

A review has recently appeared describing the synthesis of hydroazulene sesquiterpenes through rearrangement of substituted hydronaphthalene precursors, including some syntheses of guaianolides from santonin (1)... 

Because of the excellent performance of the new catalysts, many research groups use ringclosing metathesis as the key step in natural product synthesis [12]-[18]. Scheme 6 shows some examples. Via ring-closing metathesis of the olefin 37 to the hydroazulene 38, Blechert et al. [12] succeeded in synthesizing a cyclic system which is part of many sesquiterpenes. Cyclooctane derivatives, whose synthesis is the main problem in taxol synthesis, can be obtained in good yields (39 40), as demonstrated by Grubbs et al. [ 13]. 

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. 

Deliberate dehydrogenation of natural hydroazulenes and other sesquiterpene derivatives, sometimes after preceding dehydration, hydrogenation, and reduction, has been the first synthetic path to azulenes (55FCF(3)334, p. 355 59MI2, p. 301). Similar reactions yielded... 

The oxabicyclo[3.2.1]octan-2-one ring systems form a core skeleton of many naturally existing molecules. In an approach towards guaianolide sesquiterpenes, their hydroazulenic framework has been constructed through a rhodium(II)-catalyzed reaction [82] of the a-diazo ketone 106 with DMAD to afford the oxatricyclic system 107, which forms the skeleton of ambrosic acid 108 (Scheme 33). 

Proazulenes, azulenogens, hydroazulenes a group of natural cyclic sesquiterpenes, which can be terminally dehydrogenated or dehydrated to Azulenes (see). P. are chiefly compounds of the guaiane type, e.g. guaiol. 

New approaches to the hydroazulene system found in the sesquiterpene pseudoquaianolides continue to appear. Schlessinger et al. have used the route shown in Scheme 15 to synthesize (212)/ a key intermediate which was then used in syntheses of damsin (213), confertin (214), and helenalin (215). 

An attractive synthesis of the hydroazulene skeleton of the fungal sesquiterpene velleral (168) has been reported, based on the known addition of dimethyl acety-lenedicarboxylate to an enamine, viz. (166), followed by electrocyclic ring-opening of the resulting cyclobutene, viz. (167) (Scheme 31). ° The potentially useful hydro-... 

The continued search for novel synthetic routes to the sesquiterpene pseudo-guaianolides has resulted in several new approaches to the hydroazulene ring system. Lansbury and Serelis have shown that the hydroxycyclopentanone (191) undergoes facile cationic cyclization on treatment with formic acid, leading directly to the hydroazulenedione (192). Further manipulation of (192) led to the total synthesis of damsinic acid (193). In an impressive synthesis of the closely... 

It is possible to effect an anti-Markovnikov cyclization to the per-hydroazulene skeleton of the guaianes by the action of acid catalysts upon the 5,6-epoxides of various germacrene sesquiterpenes (727, 124). Markovnikov opening of the epoxode with participation of the transannular double bond (cyclobutane-like strain in transition state) does not compete. For contrast, the cyclization of the isomeric epoxide to eudesmanediol is also shown. 

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