α-Alkylation of (S)-Asparagine with Self-Regeneration of the Stereogenic Center:  Enantioselective Synthesis of α-Substituted Aspartic Acids^1,2

Abstract

A convenient method for the α-alkylation of (S)-asparagine with “self-regeneration of the stereogenic center” is described. The synthetic protocol involves stereoselective conversion of (S)-asparagine into enantiopure imino ether (2S,6S)-9, which is then alkylated with complete diastereoselectivity to give trans products 10−13 in good yields. Hydrolysis of these alkylated heterocycles is accomplished under mild acidic conditions to give the desired, enantiopure α-alkyl aspartic acids in excellent yields.

Fundamental Developments of Chiral Phase Chromatography in Connection with Enantioselective Synthesis of β‐Amino Acids

“…Consequently, given the crucial importance of b-amino acids, 181] their enantioselective synthesis became a central aim in our research group. [182][183][184][185][186][187][188] In this regard, in view of the fact that (R)-or (S)-a-amino acids can be synthesised by means of the derivatisation of glycine derivatives such as imidazolidinone 13 (Figure 10a), [189,190] a similar strategy to obtain the b-analogues starting from achiral b-alanine (Figure 10b) was developed. [191] Variations of the proposed methodology allowed the development of the enantioselective synthesis of a-substituted b-amino acids by using the (2S)tert-butyl-3-methyl-perhydropyrimidin-4-one (2S)-14 formed via (S)-asparagine.…”

1-Benzoyl-2(S)-tert-butyl-4-methoxy-6(S)-carbomethoxy-1,2,5,6-tetrahydro-1,3-pyrimidine: a useful precursor of α-alkylated aspartic acids

“…The title compound, (I), was prepared to be used as a precursor of α-alkylated aspartic acid derivatives. Similar derivatives of α-alkylated aspartic acid precursors had been synthesized before (Juaristi et al, 1998). The crystal structure of (I) was determined to prove its successful synthesis.…”

Synthesis of (2S,4S)-2-Substituted-3- (3-Sulfanylpropanoyl)-6- Oxohexahydropyrimidine-4-Carboxylic Acids as Potential Antihypertensive Drugs

“…It was found by the analysis of published data that sodium (potassium) salts of 2-substituted 6-oxohexahydropyrimidine-4-carboxylic acids formed in the reaction of the natural amino acid L-asparagine with carbonyl compounds in alkaline medium. This reaction was investigated mainly by an example of derivatives of isobutyric, trimethylacetic, and benzoic aldehydes [12]- [16]. The process was found to occur with a high stereoselectivity giving prevailingly the spatial isomer with (2R,4S)-configuration of the substituents in the pyrimidine ring.…”