Terpenoids hydroxylation

Stereospecific biotransformation is frequently observed. Bauveria sulfure-scens stereospecifically hydroxylated an azabrendane at the quaternary carbon atom (Archelas et al. 1988 Chapter 6, Section 6.1.2), while steroid and terpenoid hydroxylations are discussed in Chapter 6, Section 6.11.2. 

O Phosphorylation of the tertiary hydroxyl and diphosphorylation of the primary hydroxyl, followed by decarboxylation and simultaneous expulsion of phosphate, gives isopentenyl diphosphate, the precursor of terpenoids,... 

Hydroxylation and Baeyer-Villiger reactions carried out by monooxygenation are important in the degradation of a range of terpenoids and steroids. The aerobic degradation of limonene can take place by a number of reactions several of which involve hydroxylation at allylic positions... 

Triterpenoids (C30 compounds) are the most ubiquitous of the terpenoids and are found in both terrestrial and marine flora and fauna (Mahato et al., 1992). Diterpenoids and triterpenoids rarely occur together in the same tissue. In higher plants, triterpenoid resins are found in numerous genera of broad-leaved trees, predominantly but not exclusively tropical (Mills and White, 1994 105). They show considerable diversity in the carbon skeleton (both tetracyclic and pentacyclic structures are found) which occur in nature either in the free state or as glycosides, although many have either a keto or a hydroxyl group at C-3, with possible further functional groups and/or double bonds in the side-chains. 

The result of the retrosynthetic analysis of rac-lO is 2-hydroxyphenazine (9) and the terpenoid unit rac-23, which may be linked by ether formation [29]. The rac-23 component can be dissected into the alkyl halide rac-24 and the (E)-vinyl halide 25. A Pd(0)-catalyzed sp -sp coupling reaction is meant to ensure both the reaction of rac-24 and 25 and the ( )-geometry of the C-6, C-7 double bond. Following Negishi, 25 is accessible via carboalumination from alkyne 27, which might be traced back to (E,E)-farnesyl acetone (28). The idea was to produce 9 in accordance with one of the methods reported in the literature, and to obtain rac-24 in a few steps from symmetrical 3-methyl-pentane-1,5-diol (26) by selective functionalization of either of the two hydroxyl groups. 

The terpenes are simple lipids whose base unit is isoprene. Oxygen-containing ter-penes are called terpenoids, and terpenes with hydroxyl groups are called terpenols. Terpenes are further classified based on the number of isoprene imits in the molecule as shown in Table 22.6. Examples of terpene molecular structures are presented in Figure 22.18. 

Another heterocyclization is presented by Panifilow et al. Cyclic acetals and ethers are obtained by electrochemical oxidation of the terpenoid alcohol linalool 57 in methanol containing alkaline and sodium methoxide as electrolyt [102]. Anodic oxidation of the C(6)-C 7) double bond of linalool leads to the radical cation 58. In addition to direct methoxylation of the radical cation an attack on the hydroxyl group takes place. After a second one-electron oxidation and following methoxylation the regioisomeric cyclic acetal and a subsequent 1,2-hydride shift, the cyclic acetal 60 and the cyclic ether 61 are finally formed in yields of 16 and 24%, respectively (Scheme 13). As shown by Utley and co-workers bicyclic lactones 65 and 66 can be synthesized by anodic oxidation... 

Terpenoids are synthesised by the condensation of a series of isoprene (2-meth-ylbuta-1,3-diene) units, followed by enzymatic cyclisation by a terpene cyclase, and subsequent modification such as hydroxylation, and are grouped on the basis of their carbon chain length. Monoterpenes and sesquiterpenes consisting of ten and 15 carbon atoms, respectively, are ranked among the most important aroma compounds. Despite their diversity, all terpenoids are synthesised... 

In a recent extensive overview on the biotransformation of terpenoids by Aspergillus spp., Noma and Asakawa [92] also mentioned a sixth pathway of limonene bioconversion the hydroxylation at the C-4 position to give / -mentha-1,8-dien-4-ol (111), Fig. (20), a compound also identified earlier as one of the bioconversion metabolites of limonene with Penicillium italicum [83]. In this review, the fifth pathway, leading to isopiperitenol (113) which is further oxidised to isopiperitenone (112) and its rearrangement product, piperitenone (114) is also discussed. 

Some of these structures retain the methyl from the isoprenyl substituent, whilst in others this has been removed, e.g. alizarin from madder (Rubia tinctomm Rubiaceae), presumably via an oxidation-decarboxylation sequence. Hydroxylation, particularly in the terpenoid-derived ring, is also a frequent feature. 

FIGURE 63.1 Starting with mevalonate, carotenoids are biosynthesized by a special branch of the terpenoid pathway. The first C-40 hydrocarbon unit formed is phytoene, a carotenoid with three conjugated double bonds, which then is enzymatically desaturated to successively yield (3-carotene, neurosporene, and lycopene. Other carotenoids such as (3-carotene and oxocarotenoids are produced from lycopene following cyclization and hydroxylation reactions. Thus, lycopene is a central molecule in the biosynthesis pathway of carotenoids. 

The introduction of hydroxy and carbonyl groups at unactivated positions of terpenoids is usually accomplished by micro-organisms.35 However, recent studies have shown that rabbits can hydroxylate cedrol (72) at a remote unactivated methylene group to provide a mixture of products (73a and b) and (74a and b).36 Patchoulol (298) has also been functionalized in a similar fashion (c/. p. 90). 

A further study on the oxidation of terpenoid compounds by mammalian systems (c/. p. 62) has shown that patchoulol (298) is oxidized by rabbits to give a mixture of diol (299) and hydroxy-acid (300).129 Subsequent oxidative decarboxylation of (300) provided norpatchoulenol (301), the major odour carrier of patchouli oil. It has been suggested that a similar oxidative transformation of patchoulol occurs during the biosynthesis of norpatchoulenol in the plant.129 Cedrol (72) has also been oxidized by rabbits (c/. p. 62) and it is interesting to note that the hydroxylated products are... 

There have been a number of previous reviews on microbial oxidations of teipenes. Monoter-penes are often degraded progressively after an initial hydroxylation step, but di-, tri- and sesqui-tetpenes can be converted more selectively, to accumulate useful quantities of hydroxyla products. Less systematic work on the microbial oxidation of terpenoids has l n carried out than in the case of steroids, and therefore prediction of the regio- and stereo-chemistry is scarcely possible. 

Acyclic triteipenes can be considoed as aliphatic hydrocarbons and are a-hydroxylated by a number of microorganisms. The microbial oxidation of a variety of acyclic terpenoid hydrocarbons has been investigated by Nakajima, and although terminal alcohols can be obtained, for example pristanol (39) from pristane (38 equation 11), further oxidation can also occur. 

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