Pseudoguaianolides synthesis

A neat synthesis of bulnesene (632) has been achieved in which the key steps are an intramolecular photochemical addition and a subsequent fragmentation (Scheme 46). ° Another transformation of eremanthin (633) into estahatin (634) has been accomplished. Considerable activity in the field of pseudoguaianolide synthesis has resulted in the conversion of the previously reported bicyclic ketones (635) and (636) (Vol. 10, p. 90) into aromaticin (637), aromatin (638), and damsinic acid (639). Vandewalle and co-workers have also capitalized on earlier syntheses of key intermediates (Vol. 9, p. 151 Vol. 10, p. 89) to convert (640) into carpesiolin (641) and (642) into hysterin (643), which required structural revision as a result of this synthesis.This revision has been confirmed by X-ray analysis. Roberts and Schlessinger have... 

As both epimers are suitably functionalized for incorporating a second methyl group at C-10, they offer wide possibilities in the field of pseudoguaianolide synthesis. 

Perhydroazulenones.2 The key step in a synthesis of carpesiolin (3), a pseudoguaianolide lactone, is a regioselective ring expansion of a perhydroindanone (i) to 2 by dibromomethyllithium. 

Cycloheptane derivatives (7, 192-193). Wender et a/. have applied their cycloheptane annelation procedure to total syntheses of the pseudoguaianolides damsinic acid (1) and confertin (2). The paper describes the synthesis of 1-lithio-l-methyl-2-vinylcyclopropane, which is the annelation reagent utilized in the pseudo-guaianolide syntheses. 

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. 

Further studies on the development of synthetic routes to pseudoguaianolides have resulted in the stereospecific synthesis of ( )-ambrosin (593)/ ( )-damsin (592)/ ( )-helenalin (595)/ ° and the seco-pseudoguaianolide psilos-tachyin C (594) cf. Schemes 61 and 62). An elegant feature of these synthetic routes is the use of a common cyclopentenol intermediate (591) (R = H or CH2Ph) derived from norbornadiene (588) (Scheme 60) cf. Vol. 6, p. 90). 

This methodology is presently being used for a synthesis of the pseudoguaianolide confertin (5S) (Eq. 20). ... 

A new procedure for the conversion of a y-lactone into the corresponding a-methylene-y-lactone has been developed during a total synthesis of the pseudoguaianolide ( )-aromatin (Scheme 48). The readily-prepared complex cation (97) functions as an a-acrylic ester cation equivalent, converting cyclohexanone lithium enolate into the cis- and trans-a-methylene-y-lactones (98). ... 

Three syntheses of the pseudoguaianolide ( )-confertin have appeared. Schultz uses the oxidation of an a-trimethylsilylated furan intermediate followed by reduction to give a butyrolactone during his synthesis. In another, the lactone (216), prepared by iodolactonization of the appropriate dimethyl amide, is converted into (217), using Bredereck s reagent (Scheme 114). In the third... 

---