5-Methylcysteine derivatives

Heathcock and Parsons first converted Al-Cbz-D-alanine to both key protected (7 )-a-methylcysteine derivatives 1292 and 1293 via the c/i-oxazolidinone 1291 (Scheme Coupling 1292 with 1293 produced the dipeptide 1294. An... 

Benzamidomethyl-A -methylcysteine has been prepared as a crystalline derivative (H0CH2NHC0C6H 5, anhydr. CF3CO2H, 25°, 45 min, 88% yield as the tri-fluoroacetate salt) and cleaved (100% yield) by treatment with mercury(II) acetate (pH 4, 25°, 1 h) followed by hydrogen sulfide. Attempted preparation of S-acetamidomethyl-N-methylcysteine resulted in noncrystalline material, shown by TLC to be a mixture. ... 

The use of Trt-protected 3-iodoalanines for lanthionine synthesis is also a highly promising method for the synthesis of 3-methyl- and 3,3-dimethyllanthionines. 40 This method is based on the use of A-trityl-3-iodoalanine benzyl ester (54) and the symmetrically protected bis(Boc)-cystine-derivative dimethyl esters derived from L-t/treo-3-methylcysteine and d-penicillamine. Yields of the respective lanthionine derivatives are >80% however, enantiomeric excesses have not been determined for the 3-substituted lanthionines (Scheme 18). 

Nucleophilic substitution of the O-tosylthreonine derivatives 88 by the thioacetate anion provides a very convenient pathway for synthesizing (3-methylcysteine (89, Scheme 25).[1271... 

Methionine and its S-methyl derivative, S-methylmethionine, are probably important precursors of DMS in terrestrial regions. However, plants also produce a variety of nonprotein sulfur amino adds such as S-methylcysteine, its 7-glutamyl and sulfoxide derivatives, and djenkolic add (44). The biosyntheses and functions of these compounds are poorly understood, and mechanisms for their biodegradation may be of more than academic interest, particularly with respect to the generation of volatile sulfur compounds. 

Conversion of half-cystine residues in proteins and peptides to the S-methyl derivatives is advantageous in subsequent studies of amino acid sequence. Under the usual conditions of acid hydrolysis ( 2.1), S-methylcysteine is recovered in a 90% yield (Heinrikson 1971). The phenylthiohydantoin of S-methylcysteine is readily identified by routine thin layer chromatography procedures (Rochat et al. 1970). With the increasing use of the sequenator, PTH-S-methylcysteine offers a marked advantage over derivatives such as PTH-cysteic acid, or PTFl-carboxymethylcysteine, which have to be identified by special techniques (Edman 1960, 1970). S-methylcysteinyl residues provide a new point of cleavage for cyanogen bromide (5). 

In 1994, three total syntheses of 1187 were described by Pattenden and co-workers, ° Ehrler and Farooq," and Heathcock and Parsons." Pattenden and co-workers ° envisioned that the key step in their synthesis of 1187 would be cyclocondensation of the bis-thiazoline nitrile 1283 with the oxazole 1282 (Scheme 1.328). The authors had previously described a useful method of preparing a variety of chiral 4-methylthiazolines derived from (R)-2-methylcysteine methyl ester. ... 

In the nonprotein fraction reduced glutathione, GSH, is ubiquitous, and is commonly a mqjor constituent (Table I). The soluble fraction of plants also includes a variety of other sulfur-containing compounds that are normally present in relatively small amounts (a) Intermediates on the route to protein cysteine and protein methionine, such as cysteine, cystathionine, homocysteine, and methionine, (b) Compounds involved in methyl transfer reactions and polyamine synthesis AdoMet.t AdoHcy, and, presumably, 5 -methyl-thioadenosine. The biochemistry of the compounds in both groups (a) and (b) will be discussed here, (c) Compounds clearly related metabolically to cysteine or methionine, such as 5-methylcysteine and 5-methylmethionine. Because in certain plants these derivatives comprise a major portion of the nonprotein sulfur amino acids, they will be discussed here, (d) A number of compounds of uncertain function, the biochemistry of which has often not been clarified. Discussion of such compounds (Richmond, 1973 Fowden, 1964) is beyond the scope of this chapter. 

During germination of kidney beans, in which 5-methylcysteine is present mainly in the form of the y-glutamyl derivative, there is a net loss of over 70% of the total -y-glutamyl-5-methylcysteine. Since no increase in acidic peptides equivalent to the net loss of y-glutamyl-5-methylcysteine could be detected, it was concluded that hydrolysis rather than transpeptidation had occurred, and it was suggested (Thompson et al., 1962) that y-... 

Although these combined observations are suggestive, the function and physiological significance of 5-methylcysteine and its derivatives in plants remain to be established. 

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