Methionine derivatives

Biosynthetic studies using acetate (Ac), propionate (Pr), and butyrate (Bu) revealed the polyketide nature of aurodox which has the composition Pr(Ac)g for the goldinamine skeleton C-7 to C-25 and the composition Bu(Ac) for the C-27 to C-39 carbon chain of goldinonic acid. In contrast to the methyl branch at C-8, those at C-19 and C-21 are methionine-derived as are all remaining methyl groups (52,53). The biogenetic origin of the pyridone moiety is not clear. 

Following epPCR and saturation mutagenesis at hot spots, the o-selective hydan-toinase from Arthrobacter sp. DSM 9771 was converted into L-selective variants. The best L-selective mutant showed a value of 20% ee at about 30% conversion, compared to the WT displaying ee = 40% in favor of the D-methionine-derivative. With the help of an appropriate L-carbamoylase, L-methionine itself was produced. This academic/ industrial effort provided several selective hydantoinases of industrial interest (O May, (Degussa-Hiils), personal communication, 2005). 

Isab, A.A. and Sadler, P.J. (1977) Reactions of gold(III) ions with ribonuclease A and methionine derivatives in aqueous solution. Biochimica et Biophysica Acta, 492, 322-330. 

Scott Oakes et al. (1999a) have reported a dramatic pressure-dependent enhancement of diastereoselectivity for sulphoxidation of cysteine and methionine derivatives by using SC CO2 rather than conventional solvents. In the case of a derivative of cysteine, toluene/ methylene chloride gave a 50-50 mixture of stereoisomeric forms. With SC CO2 and tert-butyl hydroperoxide, however, 95% selectivity for just one stereoisomer was realized. 

Scheme 10.60 Borane reductions of ketones with L-methionine-derived S/N ligand.

The length of the alkylsulphide chain on the piperazine skeleton also modulates the activity. Thus, the methionine derivative (46e), shows an activity superior to (46a), while the compound without the alkylsulphide is inactive. Antagonistic activity towards PAF is also conferred by the stereochemistry of the tertiary carbon bonded to the aromatic nucleus. Hence, (46g (R) configuration) possesses an IC50 value of 0.18 pM and is 10-times more active than the corresponding (5) configuration (46h), and (46f) which has no methyl group... 

One of the best compounds of this series is the methionine-derived compound 2. It shows preferential inhibition of human a 1B construct (N-channel) with respect to a 1A (P/Q-channel) and a1E (R-channel) (Ambler et al., 1997). 

It must be concluded, however, that the stages of biosynthesis at which ring contraction and the loss of the C-12 acetate carboxyl occur are still unknown. It is open to conjecture whether introduction of the remaining five methionine derived methyl groups occurs at the isobacteriochlorin level or after extrusion of the C-20 meso- carbon. It has been shown that the CD3 groups of [CD3]methionine are transferred to all seven methylated positions without loss of deuterium. 

Holland HL, Brown FM, Lozada D, Mayne B, Szerminski WR, van Vliet AJ (2002) Chloroperoxidase-Catalyzed Oxidation of Methionine Derivatives. Can J Chem 80 633... 

The first metal(salen) complex investigated as an asymmetric phase-transfer catalyst was methionine-derived sulfonium salt 29. It was anticipated that the sulfonium salt... 

Amino acid specific Maillard products were isolated from the extracts by preparative GC or HPLC and identified by MS-, IR-, 1 H- and c-NMR-spectroscopy. Proline derived components are important constituents in bread, malt and beer. More than 120 proline specific Maillard products were characterized. Cysteine and methionine derived components were predominant in roasted coffee and meat flavors. Thirty cysteine- and twenty methionine-specific Maillard products were identified for the first time. 

Figure 8 Methionine derived components and other flavor...

In view of these many precedents it is surprising that the intramolecular displacement of the sulfur function of methionine derivatives has not been utilized for selective cleavage of methionine peptides. The method has only recently been applied to a number of methionine peptides which according to the following scheme (CXX-CXXIII) were first converted to sulfonium salts and then subjected to intramolecular (imino) lactonization and hydrolysis by short heating in water (Lawson et al., 1961). Table XV shows the strong influence of the nature of the added alkyl group on the yield in... 

INDOLMYCIN (20) is formed from pyruvate, and two enzymes active in initial stages of Its biosynthesis have been studied. They are a transaminase and aC-methyltransferase. The hypothetical route to indolmycin is by indole pyruvate, 3-methyl-indolepyruvate, indolmycenic acid (reduced alpha oxo group) and finally indolmycin which probably takes its amidine group from an arginine molecule 79. The closely related [pyrrolo (1,4) benzodiazepines] 80>81,82 antitumor antibiotics, anthramycin, tomaymycin and sibiromycin are formed from tryptophan (via the kynurenine pathway ), tyrosine and methionine-derived methyl groups 80.si.sz. 

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