Threonine alkylation

Contrary to this finding, the enolate of the threonine derivative 12 is alkylated in about 90% yield and with >95% diastereoselectivity to give the expected isomer 1376-79. 

Stereoselective formation of 3-alkyl-6-methoxy-2,5-piperazine-dione derivatives by the addition of methanol in the presence of NBS to 3-alkyl-6-alkylidene-2,5-piperazinediones was recently reported by Shin et al. 232 The asymmetric induction in this reaction was accomplished by the chiral center of a derivative of the natural proteinogenic chiral amino acid threonine. 

Such a rearrangement is not observed with glycine, alanine, 2-aminobutanoic acid or 2-amino-3-cyclohexylpropanoic acid, occurs partially with valine and isoleucine, but is complete with phenylalanine, tyrosine and threonine. By analogy with previous dediazoniation studies on 2-amino acids in acidic media,309 this rearrangement has been explained by the anchimeric assistance of alkyl (Val, lie), aryl (f he, Tyr) or hydroxy (Thr) groups during the dediazoniation process 306 for example, in the case of phenylalanine (4). 

An alternative route starting from serine 73 or threonine 68 74 makes use of diethoxy-triphenylphosphorane. Attempts to asymmetrically synthesize (25)-aziridine-2-carboxylic acid (1) by treating a, 3-dibromopropanoates with chiral amines 75 or by the Staudinger reaction from oxirane-2-carboxylic acid ester 70,76 leads to optically impure products, whereas 3-alkyl derivatives of tert-butyl aziridine-2-carboxylates can be prepared with high cis-selectivity from a-halo ester enolates and jV-trimethylsilyl imines. 77 Moreover, when optically... 

The best preventive measure against racemization in critical synthetic steps (e.g. fragment condensation, see p. 239) is to use glycine (which is achiral) or proline (no azlactone) as the activated carboxylic acid component. The next best choice is an aliphatic monoamino monocarboxylic acid, especially with large alkyl substituents (valine, leucine). Aromatic amino acids (phenylalanine, tyrosine, tryptophan) and those having electronegative substituents in the /7-position (serine, threonine, cysteine) are, on the other hand, most prone to racemization. Reaction conditions that inhibit azlactone formation and racemization are non-polar solvents, a minimum amount of base, and low temperature. If all precautions are taken, one still has to reckon with an average inversion of 1 % per condensation reaction. This means, for example, that a synthetic hectapeptide contains only 0.99100 x 100% = 37% of the fully correct diastereomer (see p. 233 f.). 

Hara in 1981 (8) reported on volatiles produced by roasting L-theanine and glucose at about 150°C for one hour. l-Ethyl-3,4-dehydropyrrolidone was the main product. Five pyrroles, three alkyl pyrazines and four furans which were identified by GC-MS and NMR are shown in Table VII. With the exception of l-ethyl-3,4-dehydropyrro-lidone these products are quite different than found from L-threonine alone. Surprisingly, l-ethyl-3,4-dehydropyrrolidone has never been found in tea aroma. 

An alkyl side chain of the second amino acid could be replaced by an ester group without losing the sweetness, e.g., L-Asp-L-Ser(Ac)-OMe (21), L-Asp-L-Ser(BtZ)-OMe (22) and L-Asp-L-Ser(BtZ)-0Et (23) were sweet. The replacement of the L-serine by L-threonine or by L-aZZothreonine resulted in bitter compounds (24, 25). These results matched that the introduction of a methyl group into a sweet peptide, L-Asp-L-Nva-OMe, resulted in a bitter substance (L-Asp-L-Ile-OMe (26)). The methyl group may block the interaction between the peptides and the sweet receptor. 

Several new ligands containing the oxazoline nucleus were synthesized in enantiopure form. Compounds of general structure 165 were obtained from L-serine or L-threonine and found application as catalysts for the zinc addition to aldehydes <03TA3292> or were derived from P-amino alcohols and used in diethylzinc addition to A -(diphenylphosphinoyl) imines <03JOC4322>. Also, compound 166 was derived from a commercially available amino acid and afforded good selectivity in allylic alkylation <03TL6469>. 

All the compounds produced a burnt sugary aroma, which became more burnt and heavy as the substituted alkyl chain increased in length. It is interesting that the ethyl substituted lactone II has a 100 times lower threshold value than that of sotolon, and that this compound has been considered to be an FIC in the protein hydrolysate. This was because it had been prepared from threonine by heating with hydrochloric acid and subsequent dehydration, hydrolysis, condensation (Aldol type) and decarboxylation, and it showed a strong curry-like or herbal aroma at concentrations higher than 1 ppm,... 

---