Monoterpenes stereochemistry

Metabolic transformations are characterized by high speed and yield, as well as high regio-, diastereo-and enantio-specificity. Errors in the stereochemistry of the molecules that serve to construct the genetic material are smaller than for the planetary motions. With secondary metabolites, however, enantiomerically inq)ure con unds are also encoimtered, typkally with monoterpenes and alkaloids from terrestrial plants even ant dal pathways in the same organism have been found, albeit as rare events (Guella 1998). 

Diaz-Marrero AR, Dorta E, Cueto M, Rovirosa J, San-Martin A, Darias J (2004) Supporting the NMR-Based Empirical Rules to Determine the Stereochemistry and Halogen Regiochemistry of Vicinal Vinyl Dihalides. Naturally Occurring Monoterpenes as Chemical Models. Tetrahedron 60 5049... 

The range of monoterpenes encountered is extended considerably by cyclization reactions, and monocyclic or bicyclic systems can be created. Some of the more important examples of these ring systems are shown in Figure 5.11. Such cyclizations would not be expected to occur with the precursor geranyl diphosphate, the E stereochemistry of the double bond being unfavourable for ring formation (Figure 5.9). Neryl PP or linalyl PP, however, do have favourable stereochemistry, and either or both... 

Actinidine (26) has been isolated from the roots and rhizomes of Valeriana officinalis L.2S Boschniakine (27) has been found in the seeds of Plantago sempervirens its absolute configuration has been established by optical rotatory dispersion comparisons with other monoterpene bases.26 Venoterpine (28) has been found in Striga hermonteca the stereochemistry is as yet uncertain.27... 

Monoterpenoid Alkaloids.—Aristotelia Alkaloids. Fruticosonine is a novel alkaloid, containing an unrearranged monoterpene unit, which occurs48 in Aristotelia fruticosa Hook, f the structure (54) (relative stereochemistry only) was deduced by X-ray crystallography, and confirmed by the synthesis of ( )-fruticosonine... 

Nerol (81) is a naturally occurring compound called a monoterpene (monoterpenes all contain 10 carbon atoms), present in oil of bergamot. Assign stereochemistry to its double bonds. 

Furthermore, the chiral discrimination of monoterpenes has been recognized as one of the most important analytical techniques in flavor chemistry and pharmacology because the optically active stereoisomers have different sensory qualities and biological activities. HPLC offers powerful techniques for separation and quantification of enantiomers because of the progressive improvement of chiral chromatographic materials and chiral detectors such as optical rotatory dispersion (ORD) and circular dichroism (CD) detectors. In contrast, determination of chiral compounds by GC typically requires coinjection of the reference compound with known stereochemistry. An HPLC system equipped with a chiral detector, on the other hand, allows direct determination of the configuration of chiral compounds.84... 

In the following sections, the plant species that are sources of monoterpenes are not recorded unless of some special significance, and similarly for points of stereochemistry, absolute configuration, reagents, and reaction conditions. 

With the preceding reviews of the enzymology of monoterpene cyclization and of model studies relevant to the cyclization process, it is possible to formulate a unified stereochemical scheme for the enzymatic cyclization of geranyl pyrophosphate (Figure 4). The proposal which follows is consistent with the implications of parallel advances in related fields, most notably the contributions of Cane (8,16,24,25,52), Arigoni (67) and Coates (68,69) on the stereochemistry of sesquiterpene and diterpene cyclizations, and of Poulter and Rilling (29,70) on the stepwise, ionic mechanism of prenyl transferase, a reaction type of which several monoterpene, sesquiterpene and diterpene cyclizations are, in a sense, the intramolecular equivalents. 

The second monoterpene alkaloid kopsone gave a molecular, ion which analysed for C11H19NO. The IR (1720 cm ) and C NMR (8 218) spectral data indicated the presence of a ketone function. Other groups indicated by the NMR spectra were two CHMe groups, an N-methyl, three methylenes (one deshielded at 8 56) and four methines (one deshielded at 8 72). These, as well as a postulated common origin of 51 and 52 from the hypothetical 9-hydroxy-skytanthine precursor 53 (Scheme 1), led to the proposed structure for kopsone. The relative stereochemistry was deduced from analysis of the H NMR spectrum. 

A new monoterpene alkaloid, kinabalurine G (330) has been obtained from the leaf extract of Kopsia dasyrachis in addition to 11 known alkaloids and the novel pentacyclic indole, danuphylline vide infra) [223]. Analysis of the spectral data allowed assignment of the gross structure as well as determination of the stereochemistry at the various centers. Kinabalurine G (330) is the AZ-oxide of 9-hydroxy-S-skytanthine, which is unknown, although a 9-hydroxy-skytanthine of unknown stereochemistry has been previously reported from Tecoma stans [224]. 

As regards the absolute stereochemistry of the monoterpene alkaloid (+)-venoterpine, the previously assigned formula (159) (1) has now been revised to the complete expression 66 by Ravao et al. (127) on the basis of chemical correlation with (-)-cantleyine (160). The chemical correlation consisted of hydrolysis of 160 with Ba(OH)2 and vacuum flash pyrolysis of the resulting carboxylic acid at 460°C to give a compound [[ajo +38° (CHCI3)], which was identical with natural venoterpine [[a]o +32° (CHCI3)]. 

When antirrhinoside (318) was reacted under the standard conditions, the dihydroxy acetate monoterpene pyridine alkaloid derivative 319 was produced cleanly in about 10% yield (224). The structure was deduced spectroscopically. An acetate group was apparent (8h 2.1 Sc 21.9,172.6) and doublets (J = 5.6 Hz) at 4.31 and 5.11 ppm. The latter showed an NOE with H-4 and was therefore assigned to H-6. X-ray crystallography affirmed the acetate group to be located at C-8 and defined the stereochemistry of C-6 and C-7 to be as shown in 319. 

A novel glycoside, taxicatin (280) was isolated from the leaves of T.baccata (215-218). The glycosides of aliphatic and aromatic alcohols, as well as of monoterpene alcohols and eugenol have been detected in Taxaceae (219). Recently we have isolated betuloside (283) from T. baccata, reported its absolute stereochemistry and have found it to possess hepatoprotective activity (220). Table 9 lists various glycosides and other sugar derivatives isolated from the genus Taxus. 

Several monoterpenes [320,321], humulene (364) [320] and zerumbone (365) [322] have been reported from the essential oil from the rhizomes of Zingiber zerumbet. The characterization and elucidation of structure 365 of zerumbone was reported later [323]. The crystal structure of zerumbone isolated from the rhizomes of Z. zerumbet was determined by single-crystal X-ray diffraction [324]. The stereochemistry of the double bonds of humulene was established by crystallographic study of its silver nitrate adduct [325, 326]. The essential oil from the rhizomes of Z. 

Direct evidence for the above proposal was obtained with the demonstration that separable cyclases derived from sage (Salvia officinalis) synthesize monoterpene olefins of opposite stereochemistry (74,76). Thus, cyclase I, of MW 96,000, converted GPP to (+)-a-pinene, (+)-camphene and (+)-llmonene of related configuration, whereas cyclase II, of MW 55,000, transformed the same achiral precursor to (-)-B-plnenc in addition to (-)-a-pinene, (-)-camphene and (-)-limonene. Extensive purification of each enzyme and differential inactivation studies ensured that each set of stereochemlcally related products was synthesized by a single, distinct enzyme (74). Since ( )-LPP had been shown to serve as a precursor for both enzymes (76) it was possible to directly assess the absolute configuration of the tertiary intermediate cyclized, by the preparation and separate testing of each enantiomer. As predicted by the general model (Fig. 3), 3R-LPP preferentially... 

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