Menthol enzymatic

In plant plastids, GGPP is formed from products of glycolysis and is eight enzymatic steps away from central glucose metabolism. The MEP pathway (reviewed in recent literature - ) operates in plastids in plants and is a preferred source (non-mevalonate) of phosphate-activated prenyl units (IPPs) for plastid iso-prenoid accumulation, such as the phytol tail of chlorophyll, the backbones of carotenoids, and the cores of monoterpenes such as menthol, hnalool, and iridoids, diterpenes such as taxadiene, and the side chains of bioactive prenylated terpenophe-nolics such as humulone, lupulone, and xanthohumol. The mevalonic pathway to IPP that operates in the cytoplasm is the source of the carbon chains in isoprenes such as the polyisoprene, rubber, and the sesquiterpenes such as caryophyllene. 

Figure 5 Initial reaction velocity V[ of the enzymatically catalyzed transesterification of ( )-menthol and isopropenyl acetate in SC-CO2 as a function of water activity aw...

After partial hydrolysis the starches lose a major part of their flavour binding properties. Examples of partially hydrolyzed starch products are dextrins (acid or enzymatic hydrolysis) and maltodextrins (generally enzymatically hydrolized). Acetaldehyde, ethanol, decanal and limonene only bind weakly to dextrins (presumably by adsorption) [22[, while ethylacetate is not adsorbed at all [1[. In the same way, alcohols (such as ethanol, propanol, butanol, pentanol and hexanol) and menthol are only weakly adsorbed on maltodextrins [11, 23]. 

Kamiya, N., Goto, M., and Nakashio, R, Surfactant-coated lipase suitable for the enzymatic resolution of menthol as a biocatalyst in organic media, Biotechnol. Prog., 11, 210-21S. 1995. 

Use as chiral auxiliary. Whitcscll1 has reviewed use of this chiral alcohol (1), particularly as compared with that of (-)-menthol and (lR)-(+)-8-phenylmcnthol. One advantage is that both enantiomers of 1 are available by resolution of trans-2-phcnyl-cyclohcxanol by means of enzymatic hydrolysis of the esters and that 2-substitutcd cyclohexanols arc readily available. Although this chiral auxiliary was used originally for control of enc reactions of glyoxylatcs, it is also useful for asymmetric alkylation of enolatcs, and for control of various cycloaddition reactions. 

A novel in vitro glucuronidation of a phenolic substrate was carried out with rat liver microsomes [22]. The method is simple, the reagent is optically pure, only the (4- )-glucuronic acid (13) is present, and the individual enantiomers are readily recovered by a simple enzymatic hydrolysis. Glucosidation with acetobromo-a-D-glucose (14) has also been used to separate the enantiomers of menthol [23]. 

Lu, Z., Chu, C., Han, Y., Wang, Y., Liu, J. 2005. Enzymatic esterification of dl-menthol with propionic acid by lipase from Candida cylindracea. J. Chem. Technol. Biotechnol. 80, 1365-1370. 

Enzymatic conversions have also found application in the resolution of racemic mixtures. When an organic synthesis involves a chiral center, one typically obtains a racemic mixture of the end products. Very commonly, chiral isomers differ in sensory properties, and one desires one enantiomer as opposed to the racemic mixture, e.g., L-menthol is the desired form of menthol. It is very diflicult to separate enantiomers by chemical means on a commercial basis (cyclodextrin-based colnnms have some utility in this application). However, a characteristic of enzymatic reactions is their stereospeciflcity, i.e., they will act on one enantiomer but not another. Thus, enzymatic processes may be incorporated into chemical synthesis to obtain a pure optical isomer. This may be done in either of two ways. 

In one approach, an ester of one chiral isomer (e.g., L-menthol) may preferentially be formed via enzymatic action [78]. Then one only has to separate the initial alcohol form (e.g., D-menthol — not esterified) of the target compound from its ester form (L-menthol ester), which is reasonably easy. The alternative approach is to chemically form esters of both enantiomers and use an enzyme to cleave the ester from one chiral form. This again leaves a mixture that is an ester and an alcohol that are readily separated. Berger et al. [42] have illustrated this process for the separation of enantiomers of karahanaenol (Figure 9.10). Gatfield et al. [79] have a recent patent on this method for the isolation of pure L-menthol. 

Unlike enzymatic reactions, microorganisms have the ability to perform multiple reactions, and they do not require cofacors for regeneration (albeit they require nutrients). They may be used to generate a flavor compound from a nonvolatile precursor (e.g., produce a lactone from castor oil), to effect the bioconversion of one volatile to another (e.g., valencene to nootkatone), or effect a chiral resolution (a racemic mixture of menthol). The primary limitation of using microoganisms for... 

More than 15 preparations described in patents are variations of the above synthetic schane. hi particular, to obtain optically pure Emtricitabine, lipase-catalyzed enzymatic resolution, as well as chiral stationary phase HPLC was used [143]. However, the most effective procedure included separation of menthyl derivatives. This method evolved significantly since the first publication (which in fact relied on separation of all the 4 possible diastereomers) [144] one of the recent multigram preparations is shown in the Scheme 37 [145]. The first step of the synthesis included formation of methyl ester 159 from glyoxalic acid and L-menthol. Reaction of 159 with 1,4-ditiane 154 gave 1,3-oxathiolane 160 as a mixture of cis diastereomers. 

Another possible approach is based on cyclodextrins, which are bucket-shaped molecules composed of six to eight glucose units and are enzymatically derived from starch. They have the capability of building protective complexes with a variety of molecules, including cosmetically relevant ones such as menthol and vitamin E. These complexes can be attached to fabrics with the help of an adhesive or a binder, which includes cross-linkable silicones, polyacrylates, polyethylene-vinyl acetate, and polyurethanes. A certain amount of binder, typically 0.25-4.0% of dry matter per weight of fabric, is required to bind the microcapsules, complexes, or loaded particles effectively to the medical textile materials. 

In 1996, Michor et al. [57] examined the resolution of racemic citronellol and menthol by enzymatically catalyzed transesterification in SCCO2. Different lipases and one esterase with various acylating reagents were employed. While the transesterification of ( )-menthol is reasonably fast and gave high enantiomeric excess, resolution of ( )-citronellol was not feasible. 

Michor et al. [58] published another study of the enzymatic racemate separation of D,L-menthol. First the enzyme (four lipases and one esterase) catalyzed the selective formation of L-menthyl acetate. Different acid esters were used (isopropenyl acetate, triacetin, n-butyl acetate). Furthermore the solubility of L-menthol and L-menthyl acetate in SCCO2 and the effects of pressure and temperature on the initial reaction rate were investigated. The solubility increased with higher pressures, but tiie reaction rate decreased. These studies show that an integrated reaction-separation prcxiess is possible. 

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