Diterpene lactone structure

Some representative Claisen rearrangements are shown in Scheme 6.14. Entry 1 illustrates the application of the Claisen rearrangement in the introduction of a substituent at the junction of two six-membered rings. Introduction of a substituent at this type of position is frequently necessary in the synthesis of steroids and terpenes. In Entry 2, formation and rearrangement of a 2-propenyl ether leads to formation of a methyl ketone. Entry 3 illustrates the use of 3-methoxyisoprene to form the allylic ether. The rearrangement of this type of ether leads to introduction of isoprene structural units into the reaction product. Entry 4 involves an allylic ether prepared by O-alkylation of a (3-keto enolate. Entry 5 was used in the course of synthesis of a diterpene lactone. Entry 6 is a case in which PdCl2 catalyzes both the formation and rearrangement of the reactant. 

Paquette, L.A., Wang, T.-Z., Wang, S., and PhiUppo, C.M.G., Enantioselective synthesis of (+)-cleomeolide, the structurally unique diterpene lactone constituent of Cleome viscosa. Tetrahedron Lett., 34, 3523, 1993. 

H. (+)-CLEMEOLIDE, THE STRUCTURALLY UNIQUE DITERPENE LACTONE CONSTITUENT OF CLEOME VISCOSA... 

The herb Cleome viscosa (syn. cleome icosandra)y which is widely distributed in India, has long been recognized by the native population to serve as a rubefaciant, vesicant, and anthelmintic agent. As a consequence of these reputed properties, three research groups undertook almost simultaneously in the late 1970 s to determine the principal active constituent of this sticky, odoriferous plant [82,83]. On the basis of the NMR, X-ray, and CD data, the substance was determined to be the macrocyclic diterpene lactone 160 and named cleomeolide. The structural features of this macrolide are unusual in several respects (a) the double bond positioned a,p to the lactone carbonyl resides at a bridgehead site, a... 

Fig. (62). Structure of an antimicrobial diterpene lactone isolated from Baccharis genistelloides...

Latrunculin B was also present in extracts of C. hamiltoni collected from the reefs off southern Mozambique. The latter specimens of C. hamiltoni also yielded two spongiane diterpene lactones (150,151) [127]. No evidence of the hamiltonins was found in extracts of the Mozambique specimens of C. hamiltoni and possibly reflects geographical variation in the organisms that make up C. hamiltonf s diet in this region of the southern African coast. The structures of both spongiane diterpenes and the hamiltonins A -E were determined from spectroscopic data while the absolute stereochemistry at C-16 in 147 was established by comparison of its CD data with those of related compounds [127]. 

The macrocyclic diterpene lactone, cleomeolide (1) was first isolated by us [9,10] in the late 1970s and its complete structure and stereochemistry were determined by means of NMR, X-ray and CD methods. Burke et al. 

Okazaki, T., A. Ohsuka, and M. Kotake Structure of diterpene lactones from Solidago altissima L. Nippon Kagaku Kaishi 1973, 584. 

Quijano, L., F.R. Fronczek, and N.H. Fischer Sesquiterpene and diterpene lactones from Melampodium leucanthum and the molecular structure of 4(5)-dihydromelampodin-B. Phytochem. 24, 1747 (1985). 

Sclareol 114 (Structure 4.35), a ditertiary glycol, is a constituent of clarysage Salvia sclarea) oil [56, 57]. The diterpene ketone sclareolide 115 and the lactone ambrox 116 are important (bio)synthetic derivatives found in clarysage extract. 

Encelin from Montanoa speciosa is inhibitory to growth and development of fungal cells of Mucor rouxii. Other cytotoxic sesquiterpene lactones from Montanoa tomentosa ssp. microcephala have been reported.45,46 A number of kaurane diterpenes and e/tf-kauranoids have been reported that are potentially useful because of their cytotoxicity against human tumor cells, anti-HIV activity, and trypanosomicidal activity.47 56 New structures are frequently discovered, and probably we will learn new effects in humans and animals in the future.57,58 Paradoxically, these plant natural products probably have specific and important effects in the plants, but we are still ignorant of these roles. 

Salvinorin A is a tricyclic trans-cis neoclerodane diterpene containing seven chiral centers. Additionally, 1 contains multiple functional groups, which include four carbonyls at C-l, C-17, C-18, and C-21. Two of the carbonyls are esters off of the C-2 and C-4 positions of the decalin core, and the C-17 carbonyl is part of a 5-lactone ring system. Additionally, 1 contains a furan ring off C-12. Along with the functionality present on 1, C-8 has been shown to undergo epimerization readily in acidic or basic conditions. Despite the molecular complexity, total syntheses of 1 have been accomplished and structural modifications have been completed. This chapter will address total synthetic attempts towards the molecule itself and synthetic methodologies developed and applied to modify the salvinorin A scaffold. 

Cembranoids, a macrocylic class of diterpene hydrocarbon were first isolated from pine oleoresins [156, 157] and the tobacco plant [158]. Since then, the structures of circa 300 naturally occurring cembranoids have been elucidated and a comprehensive compilation of these diterpenes published through 1990 has been published [159]. Known cembranoids include both hydrocarbons and oxygen-containing compounds such as epoxy, oxo, hydroxy, and lactone functions. Most congeners are polyoxygenated. 

The macrocylic diterpene alcohol, verticillol (3) was isolated from the wood of Sciadopitys verticillata Sieb. Et zucc. (Taxodiaceae) [13]. The structure of verticillol (3) was elucidated from NMR-LIS studies on it as well as its correlation to the diepoxide (14) whose structure was established by direct single crystal X-ray analysis. The absolute configuration of verticillol (3) was determined by CD data of the verticillol norketodiepoxide (15). The carbocyclic framework of verticillol (3) is somewhat akin to at of cleomeolide (1). However, the presence of the substituents(3-OH and C-8—>C-4 lactone) in appropriate positions in (1) facilitates its conversion to compounds analogous to taxane diterpenes. 

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