Diterpenoids structure determination

Solvent shifts between deuteriochloroform and benzene or pyridine in the n.m.r. have been used in diterpenoid structure determinations. The new chemical-shift reagents, such as tris(dipivaloylmethane)europium, provide useful evidence for locating C-18 and C-20 proton resonances in C-19 oxygenated diterpenoids. 

C N.m.r. spectroscopy has played a major role in structural determination in the diterpenoid series. Some further compounds in the beyerene (stachene) series have been examined and the substituent effects have been rationalized. ... 

Structure determination of the diterpenoid alkaloids (C20) has been a challenging task because of the diverse skeleta of these alkaloids. During the period ( 1962-1972), many of the structures were determined by X-ray crystal structure determination. The development of high resolution NMR and Mass spectral instruments has facilitated the structure elucidation and determination of the stereochemistry of the diterpenoid alkaloids. The structures of more than 240 naturally occurring diterpenoid alkaloids have been determined in the past twenty five years making use of, 3C NMR studies. 

Miles, C. O., Wilkins, A. L., Garthwaite, I., Ede, R. M., and Munday-Finch, S. C., Immunochemical techniques in natural products chemistry isolation and structure determination of a novel indole-diterpenoid aided by TLC-ELISAgram, J. Org. Chem., 60, 6067, 1995. 

Fujita, T., Fujitani, R., Takeda, Y., Takaishi, Y., Yamada, T., Kido, M., and Miura, I., 1984. On the diterpenoids of Andrographys paniculata X-ray crystallographic analysis of Andrographolide and structure determination of new minor diterpenoids. Chem. Pharm. Bull. 32, 2117-2125... 

Interest in the chemistry of diterpenoid alkaloids has continued, as shown by the volume of publication during the past year. In spite of the increased reliance on physical methods of structure determination, especially on X-ray crystallography and 13C n.m.r. spectroscopy, interesting chemical transformations of these complex bases have been reported. 

Clerodanes.—The X-ray structure determination of the cis -clerodane (16) has been reported.24 This confirms the stereochemistry of a number of Solidago diterpenoids which have been correlated with this lactone. Linaridial (17), an unstable cis-clerodane dialdehyde, has been isolated25 from Linaria japonica (Scrophulariaceae). A number of clerodane diterpenoids have been isolated26 from Stachys annua (Labiatae), including annuanone (18) and the corresponding saturated ketone and... 

In the following table an attempt has been made to list all diterpenoid alkaloids isolated since 1977. The references relate in most cases to their isolation, purification, and structure determination. For work on known alkaloids, especially structural revision, the review sources listed at the beginning of the chapter should be consulted. Blank spaces in the table signify that the appropriate properties have not been recorded. Only alkaloids for which a reasonably substantiated structure has been advanced are included. Entries marked with an asterisk may be artefacts. The literature has been covered up to the end of 1985, and some 1986 references have been included. The alkaloids have been arranged in order of natural source. 

The emphasis in work related to diterpenoid alkaloids has shifted from structure determination to partial and total synthesis. X-Ray crystallography played the major role in the structure work and in interpretation of unusual chemistry. However, some interesting new chemical and spectroscopic observations, and analyses of mass spectra, have been reported. 

Since last year s Specialist Report, the emphasis in the di terpenoid alkaloid field has focused on structure determination, both by X-ray crystallography and by chemical and spectral methods. Some interesting synthetic approaches to diterpenoid alkaloids have also been reported. The total volume of work on diterpenoid alkaloids reported this year, however, is much less than in Chapter 16 of last year s Report, which covered a longer period and was intended to give a background to the subject. 

The emphasis in C19 and C20 diterpenoid alkaloid research as evidenced by published accounts during the past year has shifted from synthesis to structure determination. Of particular interest are the reports of the isolation of two new C19 bases, acomonine and iliensine, having no C-1 oxygen function. The structures of delphisine and deoxydelcorine have been determined, and revisions of the structures earlier proposed for neoline, chasmanine, homochasmanine, and excelsine have appeared. The numbering systems for the lycoctonine, atisine, and veatchine skeletons are indicated in structures (A), (B), and (C), respectively. 

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). 

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

This type of diterpenoids contains C-20-non-oxygenated and C-20-oxygenated w kauranes. The latter are classified into three groups on the basis of their oxidation patterns. Table VII exemplifies representative diterpenoids of the four groups and their NMR data which are characteristic and therefore useful for structure determination. 

Chemical reactions which were useful for structure determination of enmein-type diterpenoids involve removal or chemical transformations of the functional groups which are illustrated in Scheme 6. 

Qu, J. Wang, Y-H. Li, J.-B. Yu, S.-S. Li, Y. Liu, Y.-B. Rapid structural determination of new trace cassaine-type diterpenoid amides in fractions from Erythrophleum fordii by Uquid chromatography-diode-array detection/electro-spray ionization tandem mass spectrometry and liquid chro-matography/nuclear magnetic resonance. Rapid Commun. Mass Spectrom. 2007, 21, 2109-2119. 

The physiological activity of extracts from yew species has been known for millennia. In 1856, Lucas (358) isolated a mixture of alkaloids, which he called taxine and, 100 years later, Graf (359) showed this to be a mixture of at least seven compounds. Over 250 taxane diterpenoids are now known. Paclitaxel (312) was isolated from Taxus brevifolia (the Pacific Yew) in 1967 [360, 361] and its structure determined by X-ray crystallography in 1971 (362). The discovery of its anticancer properties led to a huge amount of research into its extraction, synthesis, production, and application. Bristol-Myers Squibb trademarked the name Taxol for paclitaxel and they, other pharmaceutical companies and academic researchers have invested much into the study of pacUtaxel and the search for active analogues and prodrugs. Some of the more significant materials in this series are shown in Fig. 8.59. 

Eguren, L., A. Perales, J. Fayos, B. Rodriquez, G. Savona, and F. Piozzi New neoclerodane diterpenoid containing an oxetane ring isolated from Teucrium chamaedrys. X-ray structure determination. J. Org. Chem. 47, 4157 (1982). 

Govindan, M. (1995) Mechanism-based antitumor screening of Caribbean marine organisms isolation and structure determination of novel diterpenoids from the gorgonian Eunicea mammosa. J. Nat. Prod., 58, 1174-1184. 

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