Diterpenoids bitterness

Ginkgolide A (diterpenoid) Ginkgo biloba (maidenhair tree) (Ginkgoaceae) [root bark, leaf] [Reduces expression of adrenocortical mitochondrial PBZ-R thence corticosteroid synthesis AI, anti-asthmatic, antistress, insect antifeedant, bitter, neuroprotective]... 

A number of polyhydroxylated kaurenes (93)—(98) have been isolated " from the fern Pteris plumbaea. Some further bitter diterpenoids have been obtained ... 

Brockhoff A, Behrens M, Massarotti A, Appendino G, Meyerhof W (2007) Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and lab-dane diterpenoids, strychnine, and denatonium. J Agric Food Chem 55 6236-6243 Brouwer JN, Hellekant G, Kasahara Y, van der Wei H, Zotterman Y (1973) Electrophysiological study of the gustatory effects of the sweet proteins monellin and thaumatin in monkey, guinea pig and rat. Acta Physiol Scand 89 550-557... 

Kohno H, Maeda M, Tanino M et al (2002) A bitter diterpenoid furanolactone columbin from Calumbae Radix inhibits azoxymethane-induced rat colon carcinogenesis. Cancer Lett 183 131-139... 

Clerodendrin A, which was isolated as a bitter principle from Clerodendron tricotomum, has been assigned the structure (22) on the basis of an 2f-ray analysis of the p-bromobenzoate-chlorohydrin. The full paper describing additional work on the structure of olearin (23) has appeared. The stereochemistry at all but one centre has been determined and olearin has been interrelated with a diterpenoid of known structure from a Dodonaea species. 

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). 

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). 

In Japan, R.japonica and R. trichocarpa have been used as bitter stomachics and anthelminthics, while in China R. ternifolia has been used as an antiphlogistic, germicide, antipyretic, and toxicide and R, rubescens is used in cancer of the esophagus. Initial studies to track down the compounds responsible for the activity of Rabdosia species were carried out in 1954. Subsequent studies dealt with cytotoxicity, antitumor activity, inhibition of oxidative phosphorylation, anti-feeding activity, growth inhibitory activity, and bitterness. All of the foregoing activities have been attributed to the diterpenoid constituents. 

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. 

Ochi, M., M. Okamura, H. Kotsuki, 1. Miura, I. Kubo, and T. Kubota Bitter Diterpenoids from Rabdosia shikokiana (Makino) Hara. Bull. Chem. Soc. Japan 55,2208 (1982). 

Fujita, T, Y. Takeda, and T. Shingu Bitter Diterpenoids from Isodon shikokianus var. intermedius. Phytochem. 18, 299 (1979). 

This class of bicyclic diterpenoids derive their generic name and chirality from (-)-clerodin (402), the bitter principle from the leaves and twigs of Clerodendron infortunatum (180, 328). The oleoresin of Hardmckiapinnata contains several compounds of this class, including the simplest clerodane, kolavenol... 

Common sage and rosemary (see Table 8.32), plants of the Lami-aceae family, contain the diterpenes camosic acid, also known as rosmaricin (8-259), derived from ent-caurene, and bitter carnosol (picrosalvin, 8-260), which are potent antioxidants. Carnosic acid is a major component of fresh rosemary tops (1-2%), but is unstable and is enzymatically transformed into carnosol. These two diterpenoids represent about 15% w/w of plants haulm extracts and exhibit about 90% of extract antioxidant activity. Other transformation products of carnosic acid are rosmanol (7a-hydroxy derivative, 8-261), epirosmanol (7P-isomer, 8-262) and similar compounds. 

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