Rabdosia diterpenoids

Interconversions among Rabdosia diterpenoids have been frequently undertaken to establish the structures of new compounds, but were occasionally carried out as a matter of purely chemical interest. The following discussion is limited to interconversions between kaurene-type and 6,7-secokaurene-type diterpenes. The transformations are divided into biogenetic-type and retrobiogenetic-type chemical conversions. 

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Various biological activities, such as antibacterial and antitumor ones, and inhibitory activities as to insect growth and oxidative phosphorylation in rat mitochondria, are known for Rabdosia diterpenoids [2]. During the past decade, the antitumor activity of diterpenoids isolated from R. trichocarpa [149. 150]... 

The first investigation of the bitter principles in enmei-so was carried out in 1910 and isolation of a crystalline bitter substance was reported by Yagi (2). In 1954, antibacterial activity was reported for the extract (5). In 1958, isolation of enmein, one of the major diterpenoid constituents, initiated structure determination and investigation of other constituents. Since then, our knowledge of the diterpenoids of Rabdosia species has developed to a remarkable degree. Particular interest has centered on their antitumor activity. For previous reviews of the chemistry of Rabdosia diterpenoids, the reader is referred to Ref. (4—7). 

Tables I—IV list structures of all Rabdosia diterpenoids known at present on the basis of this classification.

For structure determination of the Rabdosia diterpenoids, spectroscopic investigations and chemical reactions are useful in general and X-ray analysis is used by necessity. 

Oxidation patterns of ring D in Rabdosia diterpenoids derived from ent-16-kaurene are classified into 5 types shown in Table VI. Each class exhibits characteristic spectral data, from which the structural features of ring D are easily deduced. Table VI shows typical UV, IR, and NMR data for a typical example belonging to each class. 

Because of their unique structures, their abundant occurrence in nature and their relative ease of isolation, the chemistry of Rabdosia diterpenoids has been studied thoroughly and many articles on their chemical behavior and transformations have been published. 

The biosynthesis of enmein (62) and oridonin (32), the major bitter principles in the leaves of Rabdosia japonica, has been investigated by E. Fujita and coworkers. It is thought to proceed by a pathway similar to that for cyclic diterpenoids in general, with e r-16-kaurene (116) as an important precursor. A biogenetic pathway and a classification of the Rabdosia diterpenoids based on the biogenesis were proposed 123). 

A qualitative theory on the relationship between bitterness and chemical structures of bitter Rabdosia diterpenoids has been proposed 143). To be bitter a substance must have at least one bitter unit it consists of a hard acid and a hard base which are located within 1.5 A of each other so that intramolecular hydrogen-bonding is possible. Cleavage of this hydrogen bond and concomitant formation of a new hydrogen bond to the receptor site are responsible for bitterness 150). For instance, isodonal (71) which possesses an a-orientated 11-OH is very bitter, while trichodonin (70), its 11 P-epimer, is not. In bitter isodonal, the distance between the 11-hydroxy proton, the donor proton, and the 6-aldehydic oxygen, the proton acceptor, is ca. 1 A, while in tasteless trichodonin it is ca. 3 A. 

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