Isoprenyl group

Reduction of the isoprenyl groups of isohumulone and p-isohumulone to tetrahydro- and hexahydro-isohumulone, respectively, increases the lipophilicity of the resultant products. A corresponding increase in their bitterness was observed. A similar increase in bitterness was reported for hydroquinine following reduction of the vinylic double bond of quinine (117). Because the stereochemistry of the quinines does not have any significant effect on the bitterness, this change must be due to change in the relative lipophilicity of the compound. 

A first approach to study the interaction of posttranslational modified Ras proteins with membranes was the analysis of binding and exchange of isoprenyl-ated peptides with and between lipid vesicles utilizing a fluorescent bimanyl label. Studies with K-Ras peptides revealed that a single isoprenyl group is sufficient for membrane association only if supported by carboxymethylation of the C-terminal cysteine [227,228]. 

A highly active zinc powder can be generated in bulk by electrolysis of a tetraalkylammonium salt in dimethylformamide between a zinc anode and a platinum cathode [183]. This reagent has been used in stoichiometric amounts for Re-formatsky-type reactions where the tribromide 61 is used as a precursor for the isoprenyl group [184]. Zinc promoted 1,4-elimination of bromine to give the butadiene system is followed by a Reformatsky reaction of the remaining allylic bromine substituent. 

In 1999, Yamamoto reported the first example of an enantioselective biomime tic polyene cychzation using chiral LBAs as artificial cyclases. The LBA cyclase is believed to participate in the initial enantioselective protonation of the terminal isoprenyl group which induces concomitant diastereoselective cychzation [128]. Subsequent work by the Yamamoto group led to the development of LBA 52 as an artificial cyclase for hydroxypolyprenoids (Scheme 5.68) [129]. LBA 52 mediated cychzation of the the appropriate achiral hydroxypolypreniods permitting the short total syntheses of (-)-Chromazonarol, (-i-)-8-epi-puupehedione, and (-)-ll -deox-ytaondiol (not shown). 

Addition of Isoprenyl Groups A number of eukaryotic proteins are modified by the addition of groups derived from isoprene (isoprenyl groups). A thioether bond is formed between the isoprenyl group and a Cys residue of the protein (see Fig. 11-14). The isoprenyl groups are derived from pyrophosphorylated intermediates of the cholesterol biosynthetic pathway (see Fig. 21-33), such as famesyl pyrophosphate (Fig. 27-30). Proteins modified in this way include the Ras proteins, products of the ras oncogenes and proto-oncogenes, and G proteins (both discussed in Chapter 12), and lamins, pro-... 

Since most P-gp effectors are hydrophobic, it was of interest to study flavonoids substituted with different hydrophobic groups, for example the isoprenyl group [210]. Isoprenylated flavonoids are natural compounds which constitute a class of plant secondary metabolites. Comte et al. [210] have synthesized a series of C- or O-substituted hydrophobic derivatives of chrysin (22). Increasing the hydrophobicity of substituents at positions 6, 7, or 8 increased the affinity of binding to the purified cytosolic domain of P-gp. Isoprenylated derivatives also increased intracellular daunomycin (78) accumulation in K562/R7 leukemic cells. 

Introduction of the isoprenyl groups at C-5 and C-7 in echinulin (115) has been shown, by the results of [5(i )-3H]- and [5(S)-3H]-mevalonate incorporations, to proceed with normal inversion of configuration at C-5 (mevalonate numbering) in the intermediate dimethylallyl pyrophosphate. The pattern of incorporation of [l,2-13C2]acetate indicates that the stereochemistry at the double-bonds is the same as that of dimethylallyl pyrophosphate.42... 

Both vitamin K2 derivatives and prenylalcohols with various lengths of isoprenyl units attached showed surprisingly low tumor-specific cytotoxicity. Among them, MK-2 (with two isoprenyl groups) and GG (with four isoprenyl groups) showed the highest tumor specificity and cytotoxicity against various tumor cell lines, with TS values of as little as 2.0, possibly due to their optimal... 

One interesting possibility emerges from the likelihood that an n-71 interaction between an oxygen lone pair of LBA and jr electrons of the terminal carbon-carbon double bond of the substrates stabilizes the transition state of the cyclization or the initial protonation step. The transition-state assembly proposed on the basis of this assumption and the steric repulsion would clearly lead to predominant approach of (i )-LBA to the si face of the terminal isoprenyl group (Fig. 4). 

Several important biomolecules are composed of nonterpene components attached to isoprenoid groups (often referred to as prenyl or isoprenyl groups). Examples of these biomolecules, referred to as mixed terpenoids, include vitamin E (a-tocopherol) (Figure 10.22a), ubiquinone (Figure 10.3), vitamin K, and some cytokinins (plant hormones) (Figure 11.11). 

Several bacterial species produce C45 and C50 carotenoids which contain one or two extra isoprenyl groups. Although their biosynthesis has not been studied, it is probable that instead of proton-initiated cyclisation at the polyene termini, attack by dimethyl allyl pyrophosphate results in substances such as the symmetrical decaprenoxanthin (P439) (68). The stereochemistry of the isolated acyclic double bond was shown to be trans by the n.m.r. spectrum of the corresponding aldehyde. Other carotenoids present in Flavobacterium... 

The diacylglycerol backbone in eubacteria and eukaryotes is sn-3-glycerol esterified at positions 1 and 2 with long-chain fatty acids (Fig. 2). In archaebacteria (Fig. 3), the opposite isomer sn-1-glycerol forms the lipid backbone and the hydrophobic domain is composed of phytanyl (saturated isoprenyl) groups in ether linkage at positions 2 and 3 (an archaeol)... 

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