Macrocyclic Diterpenoids

Marine organisms, particularly corals, have continued to be a source of novel diterpenoids. Cembrenene (72) and mayol (73) are two new cembranoid diterpenoids from the soft coral Sinularia mayi.129 The cembrene alcohol (74) has been 

Yamashita, Agric. Biol. Chem., 1981, 45, 1833. 

Garcia-Granados, A. Parra, A. Pena, A. Saenz de Buruaga, J. M. Saenz de Buruaga, and S. Valverde, Tetrahedron Lett., 1980, 21, 3611. 

Nabeya, M. Nakayama, S. Hayashi, and T. Hasa, Tetrahedron Lett., 1981, 22, 1689. 

Nakagawa, M. Kobayashi, K. Hayashi, and H. Mitsuhashi, Chem. Pharm. Bull., 1981, 29, 82. 

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Synthetic endeavours have continued in the diterpenoid series. The cyclization of geranylgeranic acid chloride to derivatives of cembrene, and their conversion into cembrene itself, have been described. Some further extensions of the route to macrocyclic diterpenoids based on the intramolecular cyclization of epoxysulphides and the subsequent modification of the macrocylic product have been described. ... 

Phorbol and its Relatives.—Jatrophone (114) is a macrocyclic diterpenoid tumour-inhibitor which has been isolated from Jatropha gossypiifolia (Euphorbiaceae). The structure was proven by Z-ray analysis of a cyclization product obtained with HBr in glacial acetic acid. Bertyadional (115) has been isolated from a Bertya species n.m.r. studies defined a large fragment of the molecule. The trienedione, which was reduced with zinc and acetic acid, underwent an isomerization in hot aqueous pyridine in which the 4(10) double bond was shifted to the 1(2) position. 

The absolute stereochemistry of mukulol (79) has been determined." The variation in 4,8,13-duvatrienediol content of tobacco leaves has been studied. " Young plants contain the highest concentration. Many terpenoid degradation products of these macrocyclic diterpenoids have been isolated from tobacco leaves. The absolute configurations of some of these, e.g. (80), have been determined. Ovatodiolide (81) and anisomelic acid (82) are two diterpenoid lactones which have been isolated from Anisomeles malabarica (Labiatae). Pukalide (83) is a furanocembranolide which has been obtained from the soft coral Simularia... 

A n.m.r. study of the 14-membered ring diterpenoids has been published. The Coelenterata have been the source of a number of macrocyclic diterpenoids. The cembranolides of marine origin have been reviewed. The structure (96) of a new sinulariolide, from Sinularia notanda, is also reported in this review. The soft coral Lobophytum crassum afforded (97)/ which is an isomer of lobophytolide, and crassolide (98). The keto-epoxide (99) and the 13-membered ring-contraction product (100) were obtained from another Lobophytum species. 

The structures of ovatodiolide (101), isolated from Anisomeles indica (Labia-tae), and of its intramolecular cyclization product (102) have been described in full. Macrocyclic diterpenoids have also been obtained from some Eremophila species. The structure (103) was assigned on the basis of an X-ray analysis to an epoxycembradienol obtained from E. george/. A cembrenetriol (104), from... 

Tobacco has been the source of a number of macrocyclic diterpenoids. The 4-epimeric thunbergadiene-4,12-diols (105) are two further members of the series. The structure of one of the epimers was determined by X-ray analysis. Further examples of nor-isoprenoids which are possible degradation products of the macrocyclic tobacco diterpenoids have been described.Two further diterpenoids, cladiellin (106) and acetoxycladiellin (107), which are related to euni-cellin, have been obtained from a soft coral Cladiella species. The structure of the latter was derived by X-ray analysis. 

Taxus alkaloids are derived from macrocyclic diterpenoid precursors. These diterpenes are derived from macrocyclic precursors (Blechert and Guenard, 1990) (see Chapter 22). Four major structural t) s of Taxus diterpenes exist (Fig. 36.11). 

Kupchan SM, Sigel CW, Matz MJ, Saenz Renauld JA et al. 1970 Tumor inhibitors. LIX. Jatrophone, a novel macrocyclic diterpenoid tumor inhibitor from Jatropha gossypiifolia. J Am Chem Soc 92 4476-4477... 

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