Monoterpene chiral

Monoterpene Chiral phase Order of elution References... 

Both a- and P-pinenes are popular starting materials for the synthesis of other monoterpene chiral synthons such as carvone, terpineol, and camphor (vide infra). Reactions leading to other monoterpenes are briefly summarized in Figure 5.1. Treatment of a-pinene with lead tetraacetate followed by rearrangement gives trans-verbenyl acetate (7), which is hydrolyzed to yield trans-verbenol (8) 8 Subsequent oxidation of 8 gives verbenone (9), which can be reduced to give cw-verbenol... 

Figure 10.3 Gas cliromatograms of a cold-pressed lemon oil obtained (a) with an SE-52 column in the stand-by position and (b) with the same column showing the five heart-cuts (c) shows the GC-GC chiral chromatogram of the ti ansfeired components. The asterisks in (b) indicate electric spikes coming from the valve switcliing. The conditions were as follows SE-52 pre-column, 30 m, 0.32 mm i.d., 0.40 - 0.45 p.m film tliickness cairier gas He, 90 KPa (stand-by position) and 170 KPa (cut position) oven temperature, 45 °C (6 min)-240 °C at 2 °C/min diethyl-tert-butyl-/3-cyclodextrin column, 25 m X 0.25 mm i.d., 0.25 p.m film thickness cairier gas He, 110 KPa (stand-by position) and 5 KPa (cut position) oven temperature, 45 °C (6 min), rising to 90 °C (10 min) at 2 °C/min, and then to 230 °C at 2 °C/min. Reprinted from Journal of High Resolution Chromatography, 22, L. Mondello et al, Multidimensional capillary GC-GC for the analysis of real complex samples. Part IV. Enantiomeric distribution of monoterpene hydrocarbons and monoterpene alcohols of lemon oils , pp. 350-356, 1999, with permission from Wiley-VCH.

Gas chromatography (GC) has also been used for preparative purposes, but is restricted to relatively volatile racemates such as anesthetics, pheromones or monoterpenes and, therefore, very few applications are reported. Nevertheless, in the cases to which GC may be applied, it could be considered as an economical alternative to HPLC. Most of the resolutions of enantiomers were performed on cyclodex-trin-derived CSPs [109, 144-153], and only on very few occasions were other chiral selectors used [153]. 

Helquist et al. [129] have reported molecular mechanics calculations to predict the suitability of a number of chiral-substituted phenanthrolines and their corresponding palladium-complexes for use in asymmetric nucleophilic substitutions of allylic acetates. Good correlation was obtained with experimental results, the highest levels of asymmetric induction being predicted and obtained with a readily available 2-(2-bornyl)-phenanthroline ligand (90 in Scheme 50). Kocovsky et al. [130] prepared a series of chiral bipyridines, also derived from monoterpene (namely pinocarvone or myrtenal). They synthesized and characterized corresponding Mo complexes, which were found to be moderately enantioselective in allylic substitution (up to 22%). 

CHIRAL- GC DETERMINATION OF ENANTIOMERIC COMPOSITION OF OXYGENATED MONOTERPENES... 

A lot of published data on the separation of enantiomers of flavors and fragrances by GC is reviewed by Chirbase/Flavor database. Table 1. summarizes the enantiomer separation of oxygenated monoterpenes on chiral stationary phases of cyclodextrin derivatives by high resolution gas chromatography. 

Table 1. Enantiomer Separation of Oxygenated Monoterpenes on Chiral Stationary Phases of Cyclodextrin Derivatives by High Resolution Gas Chromatography...

Table 1 includes many but not all, chiral stationary phases used to separate the oxygenated monoterpenes. 

Askari C, Hener U, Schmarr HG, Rapp A, Mosandl A, Stereodifferentiation of some chiral monoterpenes using multidimensional gas chromatography, Frese-nius J Anal Chem, 340 768-772, 1991. 

The reagent has one handicap only (+)-pulegone is readily available. Consequently, Oppolzer and coworkers2 have examined a number of chiral alcohols, derived from various monoterpenes, in which the hydroxyl group is similarly shielded. The endo, e/.r-diphenylmethylisoboraeol (2), obtained from ( + )-camphor, and the enantiomer, obtained from ( —)-camphor, are almost as effective as 1 as chiral adjuncts in this Diels-Alder reaction. 

Within the natural products field, the investigation of complete biosynthetic pathways at the enzyme level has been especially successful for plant alkaloids of the monoterpenoid indole alkaloid family generated from the monoterpene gluco-side secologanin and decarboxylation product of tryptophan, tryptamine [3-5]. The most comprehensive enzymatic data are now available for the alkaloids ajmalicine (raubasine) from Catharanthus roseus, and for ajmaline from Indian Rauvolfia serpentina [6] the latter alkaloid with a six-membered ring system bearing nine chiral carbon atoms. Entymatic data exsist also for vindoline, the vincaleucoblastin (VLB) precursor for which some studies on enzymatic coupling of vindoline and catharanthine exist in order to get the so-called dimeric Catharanthus indole-alkaloids VLB or vincristine [7-9] with pronounced anti-cancer activity [10, 11]. 

Toda, F., Tanaka, K., Watanabe, M., Abe, T., and Harada, N. (1995) Enantiomer Resolution by Crystallization with Chiral Host Application to Monoterpenes, Verbenone and Apoverbenone, Tetrahedron Asymm., 6, 1495-1498. 

In addition, monoterpenes can provide some useful chiral reagents, such as the pinene-based organoborane reagents for chiral reductions, which have been reviewed extensively.42 Camphor-derived organic acids such as camphenesulfonic acid can be used for the resolution of racemic bases and is a common practice in industry (Chapter 6). 

Despite their low cost and abundant availability, the applications of monoterpenes as chiral synthons or building blocks for synthesis of chiral fine chemicals on an industrial scale have lagged far behind amino acids and carbohydrates. Most of the work in this area is related to multi-step total synthesis of complex natural products in laboratory scale. With the structures of new drug candidates in the research and development pipeline of pharmaceutical companies getting bigger and more complicated, the application of more sophisticated chiral building blocks such as the terpenes will... 

All the optically active terpenes mentioned in this chapter are commercially available in bulk (>kg) quantities and are fairly inexpensive. Although many of them are isolated from natural sources, they can also be produced economically by synthetic methods. Actually, two thirds of these monoterpenes sold in the market today are manufactured by synthetic or semi-synthetic routes. These optically active molecules usually possess simple carbocyclic rings with one or two stereo-genic centers and have modest functionality for convenient structural manipulations. These unique features render them attractive as chiral pool materials for synthesis of optically active fine chemicals or pharmaceuticals. Industrial applications of these terpenes as chiral auxiliaries, chiral synthons, and chiral reagents have increased significantly in recent years. The expansion of the chiral pool into terpenes will continue with the increase in complexity and chirality of new drug candidates in the research and development pipeline of pharmaceutical companies. 

Konig, W.A., Kruger, A., Icheln, D. and Runge, T. (1992) Enantiomeric composition of the chiral constituents in essential oils. Part 1 monoterpene hydrocarbons, journal of High Resolution Chromatography 15, 184-189. 

Separation of enantiomers on chiral phases without derivatizations have been described only for a few compounds, such as monoterpenes (3). Most separations require derivatization of the enantiomers, e.g. conversion into N-containing derivatives ( ), and at present the number of available thermally-stable chiral stationary phases is limited. 

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