Hydroxylated geraniol

Geranyl acetate (a diene) takes up 2 moles of hydrogen unselectively in 48 hours to give the saturated acetate, 3,7-dimethyloctyl acetate, bp 109-110712 mm, 1.4261. (Geraniol itself has an allylic hydroxyl and appears to suffer decarbonylation under these reaction conditions.)... 

As a further example of a hydroxyl-assisted epoxidation, geraniol and nerol bearing two isolated C=C double bonds were regioselectively epoxidized with TS-1 at the 2-position (near the OH group), as reported by Kumar et al. (795). On the basis of these results, Kumar et al. (195) proposed that the transition state of the epoxidation of allylic alcohols involves coordination of the alcoholic functional group to the Ti active site and that the double bond interacts with one of the peroxidic oxygen atoms, not with the titanium site (Scheme 9). 

FIGURE 4.47 Examples (geraniol, nerol, < -unsaturated acids, and lovastatin) of cytochrome P450 catalyzed allylic hydroxylation. 

The 1-pro-7 -hydrogen is lost on oxidizing geraniol with a cell-free extract from Cannabis sativa (Vol. 7, p. 9, ref. 96), asymmetric microbial reduction of ( )-citronellal to (-)-citronelloI is reported, and callus cultures of Nicotiana tabacum selectively hydroxylate linalool, dihydrolinalool, and the derived acetates at the -methyl group [e.g. to give (59)]. ... 

In the eighties, the bioconversion of monoterpene alcohols by fungi had not been studied intensively [32]. However, a strain of Aspergillus niger was isolated from garden soil, able to transform geraniol, citronellol and linalool to their respective 8-hydroxy derivatives. This reaction was called fu-hydroxylation [39,40]. 

In the same year the biotransformation of these monoterpenes by B. cinerea in model solutions was described by another group [41]. Although the major metabolites found were co-hydroxylation compounds, it is important to note that these authors only identified the -isomers in the extracts and that some new compounds were detected that were not described by the previous group, Fig. (9). Geraniol (20) was mainly transformed to (2 ,5 )-3,7-dimethyl-2,5-octadiene-l,7-diol (53), ( )-3,7-dimethyl-2,7-octadiene-l,6-diol (54) and (2 ,6 )-2,6-dimethyl-2,6-octadiene-1,8-diol (43), nerol (14) to (2Z,5 )-3,7-dimethyl-2,5-octadiene-1,7-diol (55), (Z)-3,7-dimethyl-2,7-octadiene-l,6-diol (56), and (2E,6Z) 2,6-dimethyl-2,6-octadiene-1,8-diol (47). Furthermore a cyclisation product (57) was formed which was not previously described. Finally citronellol (4) was converted to trans- (60) and cw-rose oxide (61) (a cyclisation product not identified by the other group), ( )-3,7-dimethyl-5-octene-l,7-diol (58), 3,7-dimethyl-7-octene-l,6-diol (59) and ( )-2,6-dimethyl-2-octene-1,8-diol (34). 

Epoxidation. Oxone decomposes in the presence of a ketone (such as acetone) to form a species, possibly a dioxirane (a), which can epoxidize alkenes in high yield in reactions generally conducted in CH2C12-H20 with a phase-transfer catalyst. An added ketone is not necessary for efficient epoxidation of an unsaturated ketone. The method is particularly useful for preparation of epoxides that are unstable to heat or acids and bases.3 The acetone-Oxone system is comparable to m-chloroperbenzoic acid in the stereoselectivity of epoxidation of allylic alcohols. It is also similar to the peracid in preferential attack of the double bond in geraniol (dienol) that is further removed from the hydroxyl group.4... 

Geraniol 10 hydroxylase catalyzes the the cytochrome P450 dependent hydroxylation of geraniol at the C-10 position to commit this substrate to the formation of iridoid monoterpenoids (Fig. 8.2). In Catharanthus roseus, this intermediate is converted to secologanin for producing the tryptamine containing monoterpenoid indole alkaloids characteristic of this plant. 

Fretz, H. and Woggon, W.-D. (1986) Regioselectivity and deuterium isotope effects in geraniol hydroxylation by the cytochrome P450 monooxygenase from Catharanthus roseus (L.). G. Don. Helv. Chim. Acta, 69, 1959-70. 

A word about the synthesis of the a-series, a-geraniol (73) and a-nerol (74), is warranted because they are often intermediates in the synthesis of 1-hydroxylated compounds (e.g., some diols described below). Weiler has continued his exploitation of the dianion of methyl acetoacetate to this end. Instead of prenylation (Vol. 4, p. 461, Ref. 73) he carried out a similar series of operations by alkylating the dianion with 4-bromo-2-methyl-l-butene, thus arriving at compounds of the a-series via the keto ester 75, methylating the enol phosphate to 76. He also prepared the double methylene isomer 77 (R = COEt) of geranyl propionate from the intermediate 75. The purpose of synthesizing this propionate was to prepare the pheromone of the San Jose scale, Quadraspidiotus pernicious, which is a mixture of the propionates of 73, 74,... 

Many hydroxylated linalools [including compounds 105, 106, 108, and 110, both (Z)- and ( )-isomers], as well as the epoxides of both furanoid (109) and pyranoid (see section on pyrans) linalyl oxides, have been identified in papaya fruit (Carica papaya). At the same time, the first reported occurrence of die two linalool epoxides (112) in nature was made. These epoxides are well known to be unstable and easily cyclized (see Vol. 2, p. 165) and have been made by careful peracid oxidation of linalool. An interesting new method has now been described. While the vanadium- or titanium-catalyzed epoxidation of geraniol (25) gave the 2,3-epoxide (see above), as does molybdenum-catalyzed epoxidation with hydrogen peroxide, the epoxidation of linalool (28) with molybdenum or tungsten peroxo complexes and hydrogen peroxide led, by reaction on the 6,7-double bond, to 112. ... 

We mentioned earlier the epoxidation of geranyl acetate using the UHP method. Conventional epoxidation of geraniol using MCPBA results in the formation of a 2 1 mixture of the 6,7-epoxide and the 2,3-isomer despite the reduction in electron density at the 2,3-position caused by the allylic hydroxyl group [29]. In this connection it is interesting to note that the 2,3-epoxide is formed in a 93% yield by using an emulsion technique in which the 6,7-double bond is kept away from the MCPBA in a hydrocarbon phase [30]. 

Figure 16.1-5. Retention of configuration during the hydroxylation at C-8 of isotopically labeled geraniol.

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