5- Methylcysteine methyl ester

From the (/ )-cysteine methyl ester 22 the thi-azolidine 9 is obtained, which can be deproto-nated with LDA. The attack of the methyl iodide on the enolate takes place from the side opposite to the bulky terr-butyl group (23 10). The auxiliary chiral center is removed under acidic conditions and (/ )-2-methylcysteine methyl ester hydrochloride Sb X FICI is obtained. (S)-2-Methyl-cysteine methyl ester hydrochloride ent-5b X FlCl can be prepared in the same way from (Sl-cysteine. 

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. ... 

The starting 2-cinnamyl-4-cyano-4-methylthiazoline 1285 was prepared in three steps from (l )-2-methylcysteine methyl ester hydrochloride 1284 (Scheme 1.329). The synthesis of 1283 was accomplished by condensation of 1284 with 1285, followed by reptition of steps two and three (Scheme 1.329). For 1289 HCl (Ri = CH3), bis-Boc-(/ )-2-methylcysteine, 1286 was coupled with rac-threonine methyl ester hydrochloride followed by cyclization with Burgess reagent to afford a mixture of diastereomeric oxazolines 1288. Oxidation of 1288 with Cu(l)Br/t-butylperbenzoate (Section 1.3.1.4) proved to be more efficient than Ni02. Deprotection then yielded 1289 HCl (Rj = CH3). 

S-Methylcysteine methyl ester, L Methionine methyl ester, L... 

First, the (/f)-2-methylcysteine compound 5 is N- and S-protected and coupled with the threonine methyl ester to the hydroxyamide 57 with benzotriazole-1 -yloxy-tripyrrolidino-phos-phonium hexafluorophosphate (pyBOP) [16]. Burgess reagent [17] turns out to be the best choice for the conversion of 57 into 58. The use of Burgess reagent for the synthesis of oxazo-line was examined extensively by Wipf et al. [ 18]. For other methods of synthesizing oxazoles, which were developed in connection to the synthesis of calyculin A, see [19]. 

Sulfoxides occur widely in small concentrations in plant and animal tissues, eg, aHyl vinyl sulfoxide [81898-53-5] in garlic oil and 2,2 -sulfinylbisethanol [3085-45-8] as fatty esters in the adrenal cortex (1,2). Homologous methyl sulfinyl alkyl isothiocyanates, which are represented by the formula CH3SO(CH2) NCS, where n = 3 [37791-20-1], 4 [4478-93-7], 5 [646-23-1], 8 [75272-81-0], 9 [39036-83-4], or 10 [39036-84-5], have been isolated from a number of mustard oils in which they occur as glucosides (3). Two methylsulfinyl amino acids have also been reported methionine sulfoxide [454-41-1] from cockroaches and the sulfoxide of i -methylcysteine, 3-(methylsulfinyl)alaiiine [4740-94-7]. The latter is the dominant sulfur-containing amino acid in turnips and may account in part for their characteristic odor (4). 

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). 

The synthesis of the oxazole compound 45 starts with the coupling of the N-protected (/ )-methylcysteine compound 18 with threonine terf-butyl ester using bis(2-oxo-3-oxazolidi-nyl)phosphinyl chloride (BOP-Cl) [15] as a coupling reagent. Jones oxidation of the threonine hydroxy group leads to the ketoamide 44. The desired oxazole ring is closed by treatment with thionylchloride/pyridine. After deprotection, the oxazole, compound 45 is obtained. In the next step the oxazole compound 45 is coupled with the tris(thiazoline) compound 43 to yield the thioester 46. Now Fukuyama closes the fourth and last thiazoline ring (46 47). After conversion of the carboxylic acid function into a methyl-... 

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