Farnesol, structure

Although the term terpene once referred only to hydrocarbons current usage includes functionally substituted derivatives as well grouped together under the general term isoprenoids Figure 26 6 (page 1086) presents the structural formulas for a number of representative examples The isoprene units m some of these are relatively easy to identify The three isoprene units m the sesquiterpene farnesol, for example are mdi cated as follows m color They are joined m a head to tail fashion... 

Hydrolysis of the pyrophosphate ester group converts farnesyl pyrophosphate to the corresponding alcohol farnesol (see Figure 26 6 for the structure of farnesol)... 

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

While the structure of 4,8-dimethyldecanal may suggest a tris-norsesquiter-pene, produced upon degradation of a farnesol-precursor, it appears more likely that its biosynthesis follows a way similar to that of 4-methylnonanol starting... 

A study with houseflies (7) shows clearly that very small differences in the molecular structure can result in drastically different biological effects as exemplified in Table III by the optical Isomers (-)-limonene, a fly attractant, and (+)-limonene, a fly deterrent. A difference in oxidation state In the functional group as in citronellol, a fly attractant, and citronellal, a fly deterrent, also causes different responses. A difference in the length of the carbon chain as in farnesol (C15), a fly attractant, and geranlol (CIO), a fly deterrent, also confers different... 

Farnesol 71 (Structure 4.18) is widely distributed in flower oils such as rose, acacia and cyclamen. 

Nerolidol is isomeric with farnesol and is found in neroli oil and many other oils. Its E isomer 72 is more frequently found in nature than its Z isomer 73 (Structure 4.19). 

The typical cleavage reactions of a-substituted tetrahydrofuran derivatives made possible the structural elucidation of a degradation product obtained from the mold metabolite erythroskyrine89 and a complicated bistetrahydrofuran compound produced by isomerization of farnesol diepoxide.34... 

FPP-competitive FTIs have played a key role as nonreactive ligands in the determination of FTase crystal structures, and particularly in the conformation of the FPP moiety in binary or ternary complexes [4,63,64,84] (see also Chapter 13, Volume 29). Isotopically labeled variants of FPP have also played a more direct role in the determination of the structural characteristics of FPP, both outside and inside the FTase active site. Four bis- C-labeled derivatives of farnesol and geranylgeraniol were synthesized by the Gibbs laboratory and used to prepare the corresponding FPP and GGPP... 

The structure (1) proposed by Rilling and Epstein for presqualene alcohol, the elusive biological intermediate between farnesol and squalene, has been confirmed by three independent rational syntheses. Altman et al selected the allylic diazo-compound (2) as starting material. Addition of this to trans,trans-farnesol in the presence of zinc iodide gave a 25 % yield of presqualene alcohol (1) and its isomer (3). 

Terpenes are are a class of compounds whose chemical structures are based on a number of isoprene units , derived from the hydrocarbon CH2=C(CH3)-CH=CH2 they may themselves be hydrocarbons, but may also contain alcohol (OH), aldehyde/ketone (CO) and carboxylic acid (COOH) groups. Monoterpenes are Cm compounds derived from two isoprene units, sesquiterpenes (Cu) are derived from three isoprene units, diterpenes (C20) from four and tritepenes (C30) from six. Terpenes are widespread in plants, where they are largely responsible for the odor, and they are the major constituents of plant-derived essential oUs . Among the best known terpenes are 3-pinene (turpentine), camphor, menthol and citroneUal (aU monoterpenes) and farnesol (a sesquiterpene that is a constituent of the essential oils of many plants). Certain terpenes have important biological roles vitamin A, for example, is a diterpene, and steroid hormones have a structure related to triterpenes (and are biosynthesized by a similar route). 

Starting from the JH effect of farnesol, several workers attempted to obtain more effective derivatives by structural modification of this readily available compound. Schmialek (1963) found farnesyl methyl ether (IS) and farnesyl diethylamine (16) to be more effective than farnesol, though none of these was as effective as Cecropia JH. 

As a general rule, natural products derived from isoprenoid units arise from head-to-tail reactions of that synthon. The majority of the structures of such products built up by condensation of IPP will as a result display a branched methyl on every fifth atom in the chain. Thus, reaction of IPP (1-5) with the isomer with the internal double bond (1-6) proceeds by head-to-tail coupling with expulsion of a pyrophosphate ion. The free alcohol from the product 2-1 (Scheme 2.2) is the fragrant terpene geraniol. Reaction of 2-1 with a second isoprene unit in this case again takes place by head-to-tail reaction to afford 2-2. The free alcohol from this 15-carbon triene is known as farnesol and is generally classed as a sesquiterpene (Latin sesqui-, one and a half). The molecule is displayed in the unlikely conformation 2-2b, in anticipation of the next reaction. 

Wigglesworth [4] confirmed that farnesol and its related compounds showed the juvenoid activity against the bloodsucking bug, Rhodnius prolixus. Slama and Williams [5] found that paper products made from balsam fir, Abies halsamea, showed juvenoid activity against hemipteran bug, Pyrrhocoris apterus, and called the compound the paper factor. The chemical structure of the paper factor was identified as a methyl ester of todomatuic acid, and named juvabione (3) [6]. 

The two smaller alcohols contain a five-carbon unit, called an isoprene unit, that is present in many natural products (see page 452). This unit consists of a four-carbon chain with a one-carbon branch at carbon-2. These five-carbon alcohols can combine to give geraniol (10 carbons), which then can add yet another five-carbon unit to give farnesol (1 5 carbons). Note the isoprene units, marked off by dotted lines, in the structures of geraniol and farnesol. 

PROBLEM 15.8 Draw the structures of farnesol, retinal, squalene, and /3-carotene, and mark off the component isoprene units. Identify the unusual tail-to-tail linkage in squalene. 

The isomer has been found in cabreuva, niaouli, and neroli oils among others and the (Z)-isomer in neroli, jasmine, ho leaf, and so on. Figure 6.24 shows the structures of farnesol and nerolidol with all of the double bonds in the trans-con guration. 

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