Isoleucine component

Senecic acid (6) is produced by condensation of two molecules of isoleucine. The formation of the 10-carbon necic acid (7) is accompanied by loss of C-4-pro-R hydrogen from both isoleucine components (Wrobel, 1985). In retrorsine (3), two hydrogen atoms of (25)-isoleucine at C-13 and one of the C-15 ethylidine group are derived from C-4 methylene hydrogen atoms of (25)-leucine. These were later shown to arise by loss of 4-pro-S hydrogen (or that the atoms above at C-13 and C-15 were derived from the 4-pro-R hydrogen of L-isoleucine) (Wrobel, 1985). 

Back to a Chiral Pool Approach to the Functionalized Isoleucine Component... 

Bacitracin is produced and marketed as a mixture of at least nine water-soluble peptides. The principal (60 —80%) component is bacitracin A [22601-59-8], C33H2Q3N2y02gS. The most probable stmcture of bacitracin A is shown in Figure 1 (67,73). Bacitracin B [1402-99-9] is similar to bacitracin A except that one of the isoleucines of bacitracin A is replaced by a valine. Bacitracin F [22601-63-4], is a relatively inactive degradation... 

One of the sex pheromone components of the housefly, Musca domestica, is Z9-21 H that is found on the cuticular surface of the fly. This compound is formed by the elongation of Z9-18 CoA using malonyl-CoA and NADPH to Z15-24 CoA which is decarboxylated to form Z9-21 Hc (Fig. 3) [78-80]. Other pheromone components include an epoxide and ketone that are produced from Z9-21 Hc by a cytochrome P450 [81,82] and methyl-branched alkanes that are produced by the substitution of methylmalonyl-CoA in place of malonyl-CoA at specific points during chain elongation [83,84]. A novel microsomal fatty acid synthase is involved in production of methyl-branched alkanes in most insects [85-87]. This fatty acid synthase is different from the ubiquitous soluble fatty acid synthase that produces saturated straight chain fatty acids in that it is found in the microsomes and prefers methylmalonyl-CoA. The amino acids valine and isoleucine can provide the carbon skeletons for methylmalonyl-CoA as well as propionate [83]. 

Although not of fatty acid origin another group of scarab beetles utilizes amino acid derivatives as pheromones [119]. The large black chafer, Holotrichia parallela, uses L-isoleucine methyl ester [ 120] and the cranberry white grub, Phyllophaga anxia, uses both L-isoleucine and i.-valine methyl esters [121]. More recently L-isoleucine methyl ester, N-formyl L-isoleucine methyl ester, and N-acetyl L-isoleucine methyl ester were identified in the scarab beetle Phyllophaga elenans [ 122]. These pheromone components are obviously derived from the amino acids isoleucine and valine. 

Goss and Witkop separated each of gramicidins A,B and C into a pair of congeners and identified the major congener as valine-gramicidin and the minor component as isoleucine-gramicidin39. 

Earlier in this chapter, it was mentioned that many of the nonprotein amino acids are components of nonribosomal peptides. During such a biosynthesis, the peptide is attached to a carrier protein through a thioester bond, until chain termination occurs and the final product is released. The carrier protein is posttranslationally modified by the attachment of a phosphopantetheinyl group from coenzyme A. This step gives rise to the active carrier protein with a phosphopantetheine arm upon which amino acids are added to during NRPS. As an example, loading of isoleucine onto the carrier protein is depicted below (Scheme 5). Further details about nonribosomal peptide syntheses and enzymatic reactions can be found in Chapter 5.19. 

L-isoleucine methyl ester, N-formyl L-isoleucine methyl ester and N-acetyl L-isoleucine methyl ester. The major component of the male attractant pheromone of the scarab beetle, Holotrichia reynaudi, was identified as anisole. ... 

Pyrrolizidine Alkaloids.—The necic acid component of senecionine (8) derives from two molecules of isoleucine, radioactivity from precursor amino-acid being equally incorporated into both halves of the necic acid fragment, as shown in Scheme 2 (c/. Vol. 9, p. 4). It has now been shown that biotransformation of isoleucine into the necic acid involves loss of half of a tritium label from C-4 in each of the two amino-acid fragments.6 Removal of a proton is, therefore, stereospecific, and oxidation at C-4 does not proceed beyond the two-electron level i.e., a higher intermediate oxidation level, corresponding to a ketone, is excluded. Further results indicate that for each molecule of isoleucine it is the 4-pro-S proton [see (14)] which is lost. 

In 1963 a group of Swiss authors (12) isolated zizyphine from Zizyphus oenoplia and recognized isoleucine and proline as components. Two years later Zbiral etal. (13) proposed a complete structure which was later revised (14). Pais et al. (15) in an earlier preliminary report suggested the structure of pandamine which had been isolated from Panda oleosa. This was confirmed in 1966, and the structure of the similarly constituted pandamine was reported (17). Shortly thereafter Tschesche and co-workers (18) reported the structure of an alkaloid of this type scutianine-A from Scutia buxifolia. Since then the number of cyclopeptide alkaloids of known structure has risen to more than sixty, a figure which Klein and Rapoport had envisioned in 1968 (20). The workers at Gif-sur-Yvette and at Bonn have been in the forefront of these researches but others have made important contributions (19-26). 

In contrast to the rutelines, the melolonthine scarabs generally use terpenoid-and amino acid-derived pheromones (reviewed in Leal, 1999). For example, the female large black chafer, Holotrichia parallela Motschulsky, produces methyl (2.S, 3. Sj - 2 - am ino-3-methy lpcn tanoatc (L-isoleucine methyl ester) as an amino acid-derived sex pheromone (Leal et al., 1992 Leal, 1997). There is no direct evidence that the chafer beetles or any other Coleoptera use the shikimic acid pathway for de novo pheromone biosynthesis, but some scarabs and scolytids (see section 6.6.4.2) may convert amino acids such as tyrosine, phenylalanine, or tryptophan to aromatic pheromone components (Leal, 1997,1999). In another melolonthine species, the female grass grab beetle, Costelytra zealandica (White), the phenol sex pheromone is produced by symbiotic bacteria (Henzell and Lowe, 1970 Hoyt et al. 1971). 

More than 300 compounds had been identified in cocoa volatiles, 10% of which were carbonyl compounds (59,60). Acetaldehyde, 2-methylpropanal, 3-methylbutanal, 2-methylbutanal, phenylacetaldhyde and propanal were products of Strecker degradation of alanine, valine, leucine, isoleucine, phenyl-acetaldehyde, and a-aminobutyric acid, respectively. Eckey (61) reported that raw cocoa beans contain about 50-55% fats, which consisted of palmitic (26.2%), stearic (34.4%), oleic (37.3%), and linoleic (2.1%) acids. During roasting cocoa beans these acids were oxidized and the following carbonyl compounds might be produced - oleic 2-propenal, butanal, valeraldehyde, hexanal, heptanal, octanal, nonanal, decanal, and 2-alkenals of Cg to C-q. Linoleic ethanal, propanal, pentanal, hexanal, 2-alkenals of to C q, 2,4-alkadienals of Cg to C-q, methyl ethyl ketone and hexen-1,6-dial. Carbonyl compounds play a major role in the formation of cocoa flavor components. 

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