Cleistanthanes

Two further cytotoxic nor-diterpenoid dilactones, (73) and (74), have been isolated " from Podocarpus nagi. Nagilactone F (75) has been synthesized from podocarpic acid. Two unusual diterpenoids, hispanonic acid (76) and his-paninic acid (77), both of which possess a seven-membered ring c, have been isolated from Ballota hispanica (Labiatae). Some naphthalenic nor-diterpenoids [e.g. (78)] with the cleistanthane skeleton have been isolated from Vellozia stipitata and V. declinans. 

Examples of diterpenes with the cleistanthane and cassane skeleton have been isolated from an unidentified sterile coprophilous fungus. Sonomolide A and B (162, 163) display antifungal activity against Aspergillus fumigatus and Candida albicans but do not show antibacterial activity towards Bacillus subtilis [229]. 

C20H28O2, Mr 300.44, pale-yellow gum, [a]p -3.0 (CHCI3). A diterpene of the cleistanthane group, isolated from the roots of Cunuria spruceana (Euphorbi-aceae). S. exhibits antitumor properties. The cleistan-thanes are formed biosynthetically from pimaranes or isopimaranes by migration of an ethyl group. 

Representatives of naturally occurring cleistanthanes include (+)-13(17),15-clei-stanthadiene from Amphibolis antarctica, (+)-auricularic acid from Pogostemon auricularis (Labiatae), the antineoplastic (-)-spruceanol from Cunurea spruceana and (-)-cleistanthol from Cleistanthus schlechteri (Euphorbiaceae). 

In addition to the /-abietane skeleton, other tricyclic e /-pimarane derived ring skeletons have been reported (Figure 15) Cleistanthanes and isocleistan-thanes were detected in Brickellia eupatoriedes (JP) and erythroxanes were identified in Helichrysum refluxum (450). The absolute configuration (5R, lOR) of the Brickellia cleistanthanes is identical to that reported for the cleistanthanes of the Euphorbiaceae, but antipodal to those (5S, lOS) of the Velloziaceae (Vellozia) (Figure 16 [p. 428] 427). 

Figure 15. Proposed biogenetic routes for tricyclic e /-pimarane, e /-abietane, erythroxane, cleistanthane and isocleistanthane diterpene skeletons derived from ent-labdane precursors.

Figure 16. Cleistanthanes from Brickeiiia (Compositae) and Veilozia (Velloziaceae).

Most of the approximately ninety Brickellia (Eupatorieae Alomiinae) species inhabit the North American deserts, although three species are South American disjuncts. The diterpene chemistries of the ten investigated taxa (Table 6 [p. 441] Figure 19 [pp. 457-461]) are remarkably uniform. Normal-labdanes often characterized by novel 2a,3o -hydroxylation/esterification occur in all diterpene-producing species. In B. eupatoriedes, these 2a,3a-substituted normal-labdanes co-occurred with cleistanthanes and other eAtf-pimarane-derived skeletal types. Production of normal-labdanes together with tri- and polycyclic ewMabdane-derived skeletons is an often-repeated theme in the diterpene chemistries of Compositae taxa. 

Pinto, A.C., M.L. Patitucci, R.S. Dasilva, P.P.S. Queiroz, and A. Kelecom Pimarane and cleistanthane diterpenes from Velloziaceae absolute configuration and biomimetic conversion. Tetrahedron 39, 3351 (1983). 

Ellestad, G. A., M. P. Kunstmann, and G. O. Morton Conversion of a Pimarane Diterpene into the Cleistanthane Ring System. Chem. Commun. 1973, 312. 

---