Alanines, -substituted, preparation from

A number of new j8-substituted alanines have been prepared from unsaturated azlactones by the usual reduction-hydrolysis procedures. An interesting example is the synthesis of DL-jS-ferrocenylalanine (33). ... 

When carbonyl compounds are used as electrophiles reaction with 4-monosub-stituted-5(4//)-oxazolones affords substituted serines after subsequent hydrolytic ring opening of the initial aldol product. As an example, 4-methyl-2-phenyl-5(4//)-oxazolone 193, prepared from alanine, reacts with benzaldehyde in a base-catalyzed addition to give, after hydrolysis, a 3 1 mixture of threo- and... 

P-Elimination and then replacement reaction of an a-amino acid with a nucleophile is very attractive from the viewpoint of synthetic organic chemistry because various P-substituted alanines may be prepared from a simple a-amino acid, such as serine, and nucleophiles. A reaction catalyzed by tryptophan synthase - the formation of tryptophan from serine and indole - is one of the most well-known P-elimination and replacement reactions (Scheme 2.7). Here, an aldimine Schiff base is derived from reaction of the enzyme-bound PLP with serine, which then dehydrates to give the Schiff base of PLP with 2-aminoacrylate. Indole then adds to the vinyl Schiff base, generating tryptophan after lysine aminolysis of the Schiff base product. 

A -methoxy-A -methyl-a-enaminoketoesters were employed as synthetic precursors for the regioselective condensations with hydrazines in a microwave-assisted synthesis of ethyl 1,5-disubstituted-4-pyrazole carboxylate derivatives <06OL3219>. Protected Af(r)-substituted (S)-3-(4-methoxycarbonyl-l//-pyrazol-5-yl)alanines were prepared by acid-catalyzed cyclocondensations of chiral enaminone, available from L-aspartic acid, with hydrazine hydrochlorides <06S2376>. 

So lithium enolates react with the halide 73 by conjugate substitution. The lithium enolate of the enantiomerically pure heterocycle 74 prepared from natural alanine gives one diastereoisomer of E-75 in reasonable yield. After further manipulation the heterocycle was hydrolysed to give cyclopropanes that are glutamate antagonists.12... 

In continuation of earlier work with over-expressed enzymes from E. coli (see Vol.25, Chapter 7, ref.44), D-tagatose 1,6-diphosphate has been synthesized from dihydroxyacetone by use of a combination of several enzymes including a newly isolated tagatose 1,6-bisphosphate aldolase. An efficient synthesis of D-fructose 1,6-diphosphate by use of four enzymes in a one pot operation has been described. D-[1- C] Fructose 6-phosphate has been prepared from C-enriched formaldehyde and D-ribose 5-phosphate by a formaldehyde fixing enzyme system from Methylomonas aminofaciens, and various C-substituted D-fructose phosphates have been obtained by enzymic methods from C-substituted pyruvate or L-alanine. ... 

Kobayashi et al. also applied the catalyst to asymmetric 1,4-addition reactions of azlactones with acrylates [66]. The active a-proton of the azlactone (5(4H)-oxazolone) skeleton showed a low pKa value compared to that of the alanine Schiff bases, because the anion formed is stabilized via enol formation and aromatization. After 1,4-addition reactions with acrylates, the 2-substituted glutamic acid derivatives formed could be obtained via hydrolysis using a weak acid. It was found that Pybox 3 prepared from alaninol derivatives was effective for this reaction. The desired products were obtained in good yields with good enantios-electivities. Several amino acid derivatives containing aUcyl chains in the a-position were screened, and the leucine derivative (R = Bu) showed the best enantio-selectivity in this reaction (Table 16, entry 8). 

A -Acylamino aromatic ketones 790 can be prepared by arylation of saturated oxazolones in the presence of Lewis acids. Cyclodehydration of 790 leads to 2,5-diaryloxazoles 791. For example, saturated 5(4//)-oxazolones 789 from 7/-benzoyl-alanine or A-benzoylvaline undergo Friedel-Crafts arylation to afford substituted A-benzoylphenacylamines 790. In the presence of POCI3, 790 cyclizes to produce 5-aryl-2-phenyloxazoles 791 (Scheme 7.241). ... 

Optically pure or almost pure a-methyl a-amino acids (alanine derivatives) can be prepared by reacting 5-substituted 2,5-dihydro-3,6-dimethoxy-2-methylpyrazines 1, which are derived from alanine and various amino acids as the chiral auxiliary, with alkylating agents, followed by hydrolysis (see Table 2). 

In the synthesis of l,2,5-triazepine-l,5-diones, which are expected to mimic the structural features of or-peptidyl prolin-amides, the preparation of N2,N3-disubstituted derivatives 213a from the reaction of (Z)-alanine with the N2-substituted triazepines 213 resulted in lower yields. It has been reported that these fused triazepinediones could be elaborated to give constrained rir-peptidyl proline peptide mimetics of defined stereochemistry and sequence <1997J(P1)2297>. 

Preparative Methods the imine from (5)-alanine iV-methylamide and pivalaldehyde is cyclized by heating with benzoic anhydride to give mainly cis-(l) [(2/f,5S)-(l)] in modest yields alternatively, the imine cyclizes to the trans-substituted heterocycle by treatment with HCl in MeOH, and subsequent benzoylation produces trans-(l) [(25,55)-(l)] in high yield (eq 1). ... 

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