Homoserine lactone, hydrolysis

The sulfur atom of methionine first displaces bromide from cyanogen bromide to form a sulfonium ion (Fig. 23.39). Then attack by the proximate carbonyl group of methionine displaces the excellent leaving group, methylthiocyanate, and forms a five-membered ring called a homoserine lactone. Hydrolysis steps follow to produce two smaller peptide fragments, one containing a lactone at its car-boxy terminus. 

Azetidine-2-carboxylic acid (2) like proline gives an intense blue color with sodium nitroprusside in 10% acetaldehyde solution in the presence of sodium carbonate. 98,99 Upon usual acid hydrolysis (6M HC1, 110 °C, 24 h or more) as required for amino acid analysis, azetidine-2-carboxylic acid is completely decomposed, yielding mainly homoserine lactone, as well as other ninhydrin-positive compounds. 87,89,99 To enable an accurate quantification of this imino acid, azetidine-2-carboxylic acid peptides should be hydrolyzed by alkali (5M barium hydroxide, at 100 °C for 18 h 89 or 2 M sodium hydroxide at 110°C for 22h 100 ). There are extensive NMR spectroscopic data available 100-104 and the absolute configurations of A-acetyl-L-azetidine-2-carboxylic acid 105 and A-terf-butoxycarbonyl-L-azetidine-2-car-boxylic acid 106 have been determined by X-ray analysis. 

Homoserine lactone (XII) easily forms the diketopiperazine (XIII) which is apparently in equilibrium with the tricyclic addition product (XIV) to judge from its chemical transformations and the relative ease of hydrolysis (Fischer, 1907 Snyder, 1942). Even the lower thio analog, the diketopiperazine of cysteine (XV) opens with remarkable case to give the hydrochloride of cysteinylcysteine (Grecnstein, 1937). 

The presence of homoserine, homoserine lactone, and acid hydrolysis of ribonuclease, 50 % inactivated by iodoacetate at pH 2.8, and the poor recovery of methionine provides another example for this type of breakdown of methionine sul-fonium salts (Gundlach et al, 1959b). The same products in varying proportions were observed in the decomposition of methionine carboxymethyl-... 

Methionine carboxymethylsulfonium salts These derivatives of methionine (isomers) are prepared by treating proteins with iodoacetic acid the reaction is most specific for methionine at acid pH ( 3.5). These derivatives are not affected by performic acid oxidation (see under methionine sulfoxide), but are degraded by acid hydrolysis to give methionine, carboxymethyl-homocysteine, homoserine and homoserine lactone (Gundlach et al. 1959). 

The derivatives of methionine formed by haloketones are not stable to the usual conditions of acid hydrolysis. These sulfonium salts are degraded in three different ways. Some methionine is regenerated, some homoserine and homoserine lactone is formed and possibly the homocysteine derivative of the general structure indicated below is produced where X represents the rest of the affinity label. 

In Ramalingam and Woodard s synthesis (117) the protected aspartate semialdehyde 113 was synthesized from (2S)-aspartic acid and then converted to the labeled alcohols 115 using (R)- and (S)-alpine boranes (Scheme 33). Hydrolysis then led directly to (2S,4R)- and (2S,4S)-[4- H,]homoserine lactones 112. Since the enzyme aspartase may be used to prepare samples or (2S, 3R)-[3- H J- and (2S, 3S)-[2,3- H2]aspartate (see Section IX), the synthesis, or a modification using more direct reduction methods, could be... 

S,3/ )-[2,3- H2]Homoserine lactone 112c, Ha = Hc = H, prepared as in Section V, Scheme 35, was converted to the diketopiperazine 354 (Scheme 89). This was converted to the corresponding bromide and the bis(lactim ether) was cyclized to the spiro compound 355, He = Although the cyclization was not entirely stereospecific, hydrolysis of 355, = H, gave... 

Aldehyde 348 has been used in the synthesis of a series of iron-chelating agents. Avenic acid B (352), a minor component in the root extracts of Avena sativa, is easily synthesized in two steps by reductive amination of 348 with L-homoserine lactone hydrobromide (350) under controlled pH (6-7) followed by alkaline hydrolysis [97]. 

It is well known that sulfonium salts derived from methionine may decompose in many ways. Electron-withdrawing groups on the sulfur atom promote the breakdown of the sulfonium salt by bimolecular or intramolecular nucleophilic displacement. In the case of acetyl-methionine sulfonium derivatives (21) the displacement reaction takes place with the participation of the C-carbonyl group via a 1,5-interactipn, resulting in elimination of the dialkyl sulfide and formation of homoserine iminolactone (22) which on hydrolysis gives homoserine lactone (23) (reaction 17) . Best results are obtained when the reac-... 

Hydrolysis of met-enkephalin with GNBr yields the homoserine lactone derivative of methionine and a tetrapeptide. Using the information in Exercise 27.50, what is the structure of met-enkephalin ... 

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