Costunolide synthesis

The intramolecular Hiyama reaction is excellently suited for the construction of carbocyclic and heterocyclic ring systems of different size. In most examples, problems of induced diastereoselectivity are involved (Sections 1.3.3.3.9.2.2. and D.2.3.). In the total synthesis of the antitumor germacranolide ( )-costunolide from ( ,.E)-farnesol, the correctly substituted ( , )-cyclodecadiene moiety was constructed by an intramolecular Hiyama reaction22. 

A related reaction has been described by Kitagawa and coworkers in which (126) exclusively provides (127) upon treatment with CrCb-LAJH (equation 51). The relative stereochemical result is qualitatively identical to that reported by Still and Mobilio. Cyclodecadienol (127) was subsequently transformed into ( )-costunolide. A third example of a related chromium-initiated cyclization was reported by Takeshita and coworkers in a synthesis of cycloaranosine (115). Serial treatment of (128) with MsCl/pyridine and CrCb-LAH provid (129) stereospecificaUy in 95% yield (equation 52). Another example of internal addition of an allylic chromium reagent to an aldehyde has been reported by Oshima and coworkers and is outlined in Section 1.6.3.6. ... 

We have described the chemistry of some selected sesquiterpenes which have been classified as phytoallexins. We would to apologize for unintentional omission of any important information in this review, which we tried to make as comprehensive as possible. A variety of synthetic reactions has been used to achieve the total synthesis of these phytoalexin sesquiterpenes. The isolation and biological activity of these sesquiterpenes have been discussed. It is necessary to mention that Takasugi et al.81 have reported for the first time costunolide is an antifungal sesquiterpene which inhibited spore germination of Ceratocystis fimbriata at concentration of 32 pg/ml. Many diterpenes and flavonoides have been also listed as phytoallexins. It is hoped that the research workers would find some useful information in this article. It is safe to predict from discussions in this article that many organic chemists would try to isolate antifungal sesquiterpenes. 

Rodrigues, A. A, Garcia, M., and Rabi, J. A (1978) Facile biomimetic synthesis of costunolide-1,10-epoxide, santamarin and reynosin. Phytochemistry 17, 953,954. 

Specific examples of the synthesis of natural products containing a-methylene-butyrolactone functions are to be found in the full reports from Danishefsky s group" and from Grieco s group " on the total synthesis of ( )-vernolepin (79) and its isomer, vernomenin Grieco et al. have also reported a synthesis of ( )-desoxyvernolepin " and demonstrated the use of the selenenation method for the introduction of an a-methylene substituent with a neat total synthesis of (+)-costunolide (80) from santonin," together with a general, stereochemically-... 

Shaligram A M, Rao A S, Bhattacharyya S C 1962 Terpenoids. XXXII. Absolutse configuration of junenol and laevojunenol and synthesis of junenol from costunolide. Tetrahedron 18 969-977... 

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