Sesquiterpenes, eremophilane

This Sakurai reaction has been used for a stereoselective synthesis of nootkatone (2),4 an eremophilane sesquiterpene. Thus the trienone 1 cyclizes to 2 at 0° in the presence of C2H5A1C12 in 50% yield. TiCl4 and BF3 0(C2H5)2 are less effective catalysts (28% and 23% yields of 2). 

H239-A 47, a new eremophilane sesquiterpene was isolated from a marine-derived xylariaceous fungus, showed cytotoxicity toward a variety of cancer cell lines (mean IC5o= 3.2 pg mL" ) and with some selectivity for a CCRFCEM leukemia line (IC5o= 0.9 pg mL ). ... 

P. roqueforti that produce toxic metabolites which include the tremorgenic indoles and a group of sesquiterpenoids. PR Toxin (5.34) and the eremofortins are the best known of these highly oxygenated eremophilane sesquiterpenes. 

Eremophilane sesquiterpenes are not widely distributed in Eremophila species. In fact, the only other example so far known is the aldehyde (70) which occurs in E. rotundifolia (66). The structure of 70 was deduced largely from H- and C-nmr spectral data and, the absolute, stereochemistry by correlation with eremophilone. The keto aldehyde was reduced with sodium borohydride-cerium trichloride to give a mixture of diastereomeric diols. The major compound was assigned the 9a-configuration. The derived diacetate, on treatment with lithium-diethylamine, gave mainly the 9-allylic alcohol which was oxidised to eremophilone with Collin s reagent. 

The origin of eremophilane sesquiterpenes by migration of a methyl group from C-10 to C-5 in an eudesmane intermediate has been postulated to reconcile the apparent deviation of eremophilanes from the isoprene rule (Cane, 1990). (— )-Aristolochene (12), an eremophilane-type sesquiter-... 

Several of the earlier syntheses of eremophilane sesquiterpenes have utilized the Robinson annelation reaction as a key step ". However, the synthesis of nootkatone outlined below is based on acid catalyzed rearrangement of the Diels-Alder adduct (B), directly available from a 1-methoxycyclohexa-l,4-diene (A), to a 4-substituted cyclohexenone which undergoes ring closure in formic acid to give the desired eremophilane skeleton. 

Dunham and Lawton have suggested an alternative biogenesis for the eremophilane sesquiterpenes via a series of four decalyl spiro rearrangements, a process which effectively shifts the position of the methyl group from one angular position to the other (238). This proposal has the disadvantage of requiring a cw-fused eudesmane precursor, a known (occidentalol), but rare stereochemical variant, and, at least in the case of capsidiol is excluded by recent biosynthetic results (229). 

This reaction was used to prepare an intermediate suitable for synthesis of the sesquiterpenes a- and p-eremophilane and related structures.306... 

Kingston DGI, Rao MM, Spittler TD, Isolation and structure determination of fluorensic acid, a new sesquiterpene of the eremophilane type. Tetrahedron Lett... 

Figure 10.8 Famesyl diphosphate (FPP) can be cyclized in many different ways by sesquiterpene synthases giving rise to different classes of sesquiterpenes. The eremophilane class of sesquiterpenes has received considerable attention because the genes coding for the corresponding synthase enzymes were the first to be isolated. 25...

Figure 10.9 Each class of sesquiterpenes (see Fig. 10.8) consists of many structural variants that arise from stereochemical positioning of methyl groups and sites of double bond formation. Depicted are the possible variants within the eremophilane class of sesquiterpenes, which are hypothesized to arise from an equally related class of sesquiterpene synthases. Only those structural derivatives that have been found in nature or synthesized are denoted by name. The remaining structures should, therefore, be considered novel.

Both (+)-nootkatone (566) and its (+)-4-isomer (565) have been synthesized from (+)-nopinone (564) (Scheme 69). ° On the other hand, Hiyama et have used a completely different approach for the synthesis of nootkatone (566) (Scheme 70) which involves as a key step the acid-induced cyclopentenone annulation. In an alternative route to eremophilane and valencane sesquiterpenes, NM et have used a stereoselective intramolecular Diels-Alder... 

Biogenetic schemes have been postulated to account for those sesquiterpenes which can be formally related to a eudesmane-type precursor via a 1,2-methyl migration (see Scheme 4). Thus, the skeletal and stereochemical features exhibited by the eremophilane-type (281) sesquiterpenes can be rationalised in terms of a precursor such as the cation (278), derivable from (277). By similar reasoning. 

Rao et al. isolated ishwarone (391) as one of the chief constituents of the roots of A. indica [347], Subsequent investigations by Ganguly et al. and Govindachari et al. led to the first structural assignment of ishwarone (391) as a novel tetracyclic sesquiterpene ketone based on eremophilane skeleton, the first of its kind to occur in the nature [348,349]. Ishwarane (388), reported from the roots of A. indica by Govindachari et al. is the first tetracyclic sesquiterpene hydrocarbon based on the eremophilane skeleton [334], A tetracyclic sesquiterpene alcohol, ishwarol (389) is also reported from the roots of A. indica [350]. Pakrashi et al. isolated (125)-... 

Several papers have concerned syntheses of terpenoids. The skeleton of sesquiterpenes such as eremophilane has been constructed by Naf etal. from the dienone (45), and Taber and Gunn have described a synthesis of ( )-torreyol (47) as outlined from the enone (46). Wilson and Mao have provided a further paper on their use of the intramolecular Diels-Alder reaction in the synthesis of diterpenes. 

Contents C. R. ENZELL, I. WAHLBERG, and A. J. AASEN, Iso-prenoids and Alkaloids of Tobacco - A. R. PIN DER, The Chemistry of the Eremophilane and Related Sesquiterpenes - D. GROSS, Phyto-alexine und verwandte Pfianzenstoffe - K. H. OVERTON and D. J. PICKEN, Studies in Secondary Metabolism with Plant Tissue Cultures - D. P. CHAKRABORTY, Carbazole Alkaloids - J. JACOB, Burzeldriisenlipide - W. VOELTER, Hypothalamus-Regulationshor-mone - Author Index - Subject Index. 

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