The Clerodane Series

Kusumoto, T. Okazaki, A. Ohsuka, and M. Kotaki, Bull. Chem. Soc. Japan, 1969, 42, 812. 

The widespread occurrence of the clerodane skeleton is exemplified by the isolation of (—)-hardwickiic acid (25), the C-15 monomethyl ester of kolavenic acid, and two furanoid substances, agbaninol (26, R = H) and agbanindiol B (26, R = OH) from Gossweilerodendron balsamiferum (Caesalpiniaceae). Agbanindiol A has the structure (27). These compounds have been correlated with kolavenic acid and hardwickiic acid. 

Chettaphanin-1 (28), from Adenochlaena siamensis (Euphorbiaceae), represents an interesting intermediate stage in the formation of the clerodane skeleton in which C-10 but not C-4 methyl migration has occurred. The structure of this diterpene was based on dehydrogenation of the corresponding tetra-ol to 1,2,5-trimethylnaphthalene and formation of a trienone (29) by dehydration and dehydrogenation. 

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The Clerodane Series.—Some further contributions have been made to the chemo-taxonomy of Cistus species. Whereas C. labdaniferus contains mainly labdanes such as labdane-8a,I5,l9-triol, C. monspeliensis contains a group of clerodane diterpenoids whose structures are summarized in (17), together with labdanolic acid and labdane-8a,15-diol. 

Tashmukhamedova MA, Mukhina OA, Syrov VN, Khushbeiktova ZA, Katkova SP, Kosovskii MI (1992) Hypoglycemic activity of bicyclic diterpenoids of the clerodane series as compared to adebit and maninil. Problemy Endokrinologii 38(l) 48-50 (in Russian)... 

Leonurus cardiac (Labiatae) contains some diterpenoids which have been provisionally assigned clerodane structures such as (50). Diasin (51) is a c/5-labdane related to the clerodanes which has been isolated from Croton diasii (Euphorbiaceae). Its structure was determined by and C n.m.r. spectroscopy. A series of furanoid nor-diterpenoids has been isolated from Dioscorea bulbifera (Dioscoreaceae). The structures of the diosbulbins D, E, F, G, and H, (52)—(56), were determined" by a series of spectral and chemical studies and that of diosbulbin G (55) was confirmed" by an X-ray analysis. 

Chettaphanin II, isolated from Adenochlaena siamensis, has been assigned the unusual structure (13), which was confirmed by an 2f-ray analysis. The compound can be formed in vitro by the base-catalysed condensation of dihydro-chettaphanin I. The crystal structure of tinophyllone (14), isolated from the roots and bark of Tinomiscium philippinense, has been determined by the direct method, whilst o.r.d. has been used to assign the absolute configuration. Like columbin, which occurs in a related species, it belongs to the cis-A/B-fused clerodane series. 

Although the absolute configuration of these clerodanes from Croton species was not determined, the absolute stereochemistry of a number of clerodanes from Teucrium (Labiatae) species has been clarified.39 19-Acetylgnaphalin and iso-fruticolone were shown to belong to the neoclerodane series. Teuflin (24) has been obtained40 from Teucrium viscidum and details of an X-ray structure have been published.41 The structure (25), without absolute configuration, was assigned42 to... 

In contrast to the normal-clerodanes, both cis- and trans-fuscd e clerodanes are well documented (Figure 3, Nos. 50 and 46, respectively). Mechanistically, the proposed steps of c /-clerodane biogenesis differ from those of the normal-series only in the opposite orientation of the corresponding migrating hydride or methyl group (Figure 10). 

Figure 35. Original trans ent-c txodmt structures assigned as the elongatolide series from Solidago elongata (18) and the solidagolactone series from S, altissima (413) and the revised 5a,10a-c/s-normal-clerodane structures (401, 402).

Teuflin, from Teucrium flavum (Labiatae) has been assigned the stereochemistry (39) epimeric at C-10 to teucvidin on the basis of an X-ray analysis. Isocrotocaudin (40) from Croton caudatus (Euphorbiaceae) is an 11(12)-dehydro-derivative which is similar to crotocaudin and teucvidin. The c.d. curves of the a/3-unsaturated lactones have been used to assign the absolute stereochemistry in this series. Plaunol A (41) and plaunol B (42) are anti-ulcer diterpenoid lactones which have been isolated from the Thai medicinal drug Croton sublyratus (Euphorbiaceae). Baccharis genistelloides (Compositae) has afforded a clerodane dilactone (43) similar to that isolated previously from B. trimera. 

A number of these compounds have insect antifeedant activity. The total synthesis of the substituted c/s-decalin (26) as an antifeedant has been reported. Clerodanes have previously been detected in Salvia (Labiatae) species. The gesnerohlins A and B, obtained from S. gesneraefolia, have been assigned the structures (27) and (28) although their absolute stereochemistry was not determined. A further series of clerodanes of uncertain stereochemistry has been isolated from Baccharis species, including bacrispine (29) from B. crispa and the malonate ester (30) from B. tricuneata. ... 

Diterpenes of this series are formed by rearrangement of the labdane skeleton during cyclization (Hanson, 1991 West, 1981) (Fig. 22.11). Many highly oxygenated diterpenes of this series are found in the Lamiaceae and Verbena-ceae. There are over 400 known clerodanes many of these are from Teucrium species (Lamiaceae) (Hanson, 1991). 

McCrindle and coworkers (386) have proposed a conformation for the 5/3,10/8-CK-clerodanes (Figure 58 [p. 539]). The H-20 chemical shifts for the members of this series (Table 14) are consistent with the depicted axial arrangement for this methyl. A comparison of the values reported for the cistodioic acid series of compounds (Figure 59 [p. 540] 33, 469) and those of the Compositae (Table 14) suggest that the range of observed C-9 methyl chemical shifts results largely from differences in the sidechain moiety. A saturated sidechain is correlated with the relatively upfield values, while the ftiryl sidechain is associated with the most downfield. 

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