139344-73-3

Upstream product

• 112979-39-2 methyl N-benzoyl-DL-β-homoalaninate 
• 113806-44-3 Boc-[(S,S)-β^2,3-hAla]-CO2Me 
• 98-88-4 benzoyl chloride 
• 623-43-8 crotonic acid methyl ester 
• 83509-86-8 N-benzoyl-3-aminobutyric acid 
• 74-88-4 methyl iodide 

Downstream Products

• 120134-14-7 (2R,3R)-2-Benzoylamino-3-hydroxy-2-methyl-butyric acid methyl ester 

Relevant academic research and scientific papers

Synthesis and ring opening of methyl 2-alkyl-3-(alkyl/aryl)-1- benzoylaziridine-2-carboxylates: Synthesis of polysubstituted amino acids

A new method for the preparation of 2,2,3-trisubstituted methyl 1- benzoylaziridine-2-carboxylates is reported. These compounds have been obtained starting from α-alkyl β-amino acids by formation of the lithium dianion and reaction with iodine. The aziridines undergo ring expansion or ring opening, depending on the substituents of the aziridine ring and on the reaction conditions. Following these methods, both α-substituted α-hydroxy β-amino acids and α-substituted β-hydroxy α-amino acids have been synthesised.

A facile and stereocontrolled synthesis of syn-α-alkyl α-hydroxy β-amino acids

The diastereoselective synthesis of syn-α-alkyl α-hydroxy β-amino acids 4a-h was easily accomplished by reaction of the sodium dianion of the corresponding anti α-alkyl β-benzoylamino acid methyl esters with iodine. The intermediate α-iodo derivatives spontaneously afforded cis-oxazolines which, upon hydrolysis, provided the desired products, with diastereoselectivities up to 99:1.

170. Probing the helical secondary structure of short-chain β-peptides

Structural prerequisites for the stability of the 31 helix of β-peptides can be defined from inspection of models (Figs. 1 and 2): lateral non-H-substituents in 2- and 3-position on the 3-amino-acid residues of the helix are allowed, axial ones are forbidden. To be able to test this prediction, we synthesized a series of heptapeptide derivatives Boc-(β-HVal-β-HAla-β-HLeu-Xaa-β-HVal-β-HAla-β- HLeu)-OMe 13-22 (Xaa = α- or β-amino-acid residue) and a β-depsipeptide 25 with a central (S)-3-hydroxybutanoic-acid residue (Xaa = -OCH(Me)CH2C(O)-) (Schemes 1-3). Detailed NMR analysis (DQF-COSY, HSQC, HMBC, ROESY, and TOCSY experiments) in methanol solution of the β-hexapeptide H(-β-HVal-β-HAla-β-HLeu)2-OH (1) and of the β-heptapeptide H-β-HVal-β-HAla-β-HLeu-(S,S)-β-HAla(α Me)-β-HVal-β-HAla-β-HLeu-OH (22), with a central (2S,3S)-3-amino-2-methylbutanoic-acid residue, confirm the helical structure of such β-peptides (previously discovered in pyridine solution) (Fig. 3 and Tables 1-5). The CD spectra of helical β-peptides, the residues of which were prepared by (retentive) Arndt-Eistert homologation of the (S)- or L-α-amino acids, show a trough at 215 nm. Thus, this characteristic pattern of the CD spectra was taken as an indicator for the presence of a helix in methanol solutions of compounds 13-22 and 25 (including partially and fully deprotected forms) (Figs. 4-6) The results fully confirm predicted structural effects: incorporation of a single 'wrong' residue ((R)-β-HAla,β-HAibs (R,S)-β-HAla(α Me), or N-Me-β-HAla) in the central position of the β-heptapeptide derivatives A (see 17, 18, 20, or 21, resp.) causes the CD minimum to disappear. Also, the β-heptadepsipetide 25 (missing H-bond) and the β-heptapeptide analogs with a single α-amino-acid moiety in the middle (13 and 14) are not helical, according to this analysis. An interesting case is the heptapeptide 15 with the central achiral, unsubstituted 3-aminopropanoicacid moiety: helical conformation appears to depend upon the presence or absence of terminal protection and upon the solvent (MeOH vs. MeOH/H2O).

194. Diastereoselecktive Alkylation of 3-Aminobutanoic Acid in the 2-Position

The enantiomerically pure 3-aminobutanoic acids (R)- and (S)-6 are readily available by preparative HPLC separation of the two diastereoisomers 5 obtained from addition of (S)-phenethylamine to methyl crotonate and subsequent hydrogenolysis (Scheme 2). (S)-methyl 3-(benzoylamino)butanoate ((S)-3) is also available by enzymatic kinetic resolution with pig-liver esterase.The N-benzoyl- and N-benzyloxycarbonyl derivatives rac-3, 8,and 9 of 3-aminobutanoates are doubly deprotonated with LDA and alkylated or aminated in high selectivity (17 examples, relative topicity like; see Tables 1 and 2).The configuration of three of the products is assigned (Schemes 4-6), and in four cases, the free α-substituted β-amino acid is prepared by acidic hydrolysis (see Table 3).It is shown that the doubly lithiated β-amino-acid derivative is solubilized, and its reactivity may be strongly influenced by the presence of 3 equiv. of LiCl.

α-ALKYLATION OF β-AMINOBUTANOATES WITH lk-1,2-INDUCTION

Dilithiated methyl- or ethyl-N-benzoyl-3-aminobutanoates are alkylated or added to benzaldehyde to give products of l- and u,u-configuration respectively.Several methods are presented by which enantiomerically pure 3-aminobutanoic derivatives can be prepared.