Asymmetric synthesis of β-N-substituted α,β-diamino acidsvia a chiral complex of NiII with a dehydroalanine derivative

α,β-Diamino Acids: Biological Significance and Synthetic Approaches

“…The presence of chiral ligand 252 in the complex provides a high facial discrimination for the attack of an amine affording the Re adduct 251 in diastereomeric ratios ranging from 90:10 to 97:3 depending on the nature of the reacting amine. After crystallization of the mixtures, treatment under acidic conditions allowed for the synthesis of the enantiopure ( S )-α,β-diamino acids and the recovery of the chiral ligand 252 . In another asymmetric example, optically active oxazolidinone 253 was used as Michael donor in the addition to 2-chloro-2-cyclopropylideneacetates 254 affording Michael adducts 255a with excellent trans selectivity (Scheme ).…”

“…After crystallization of the mixtures, treatment under acidic conditions allowed for the synthesis of the enantiopure (S)-R,β-diamino acids and the recovery of the chiral ligand 252. 188 In another asymmetric example, optically active oxazolidinone 253 was used as Michael donor in the addition to 2-chloro-2cyclopropylideneacetates 254 affording Michael adducts 255a with excellent trans selectivity (Scheme 48). After separation and reductive dehalogenation, two diastereomeric cyclopropyl acetic acid derivatives 255b were obtained.…”

Advances in Asymmetric Amino Acid Synthesis Enabled by Radical Chemistry

“…[5][6][7][8]13] Later, Belokon group introduced a chiral Ni(II) complex of the dehydroalanine Schiff's base with (S)-BPB -(S)-23 a -as a suitable electrophilic substrate for the conjugate addition with different nucleophiles to yield the corresponding diastereomeric complexes with a very high diastereocontrol. [117][118][119][120][121][122][123] In the subsequent work, the authors applied a chiral dehydroalanine Ni(II) complex (S)-23 a as an olefin type substrate for the conjugate addition of in situ generated radicals providing the β-substituted α-aminopropanoic acid derivatives (S,S)-24 (Scheme 14). [87] The addition of the alkyl radicals generated by AIBN and Bu 3 SnH to double bond in the ligand sphere of a Ni(II) complex (S)-23 a gave a mixture of diastereoisomeric complexes (S,S)-24 and (S,R)-24 with 40-90% diastereoselectivity in high yields (up to 90%) ( Scheme 14).…”

“…Later, Belokon group introduced a chiral Ni(II) complex of the dehydroalanine Schiff's base with ( S )‐ BPB – ( S )‐ 23 a – as a suitable electrophilic substrate for the conjugate addition with different nucleophiles to yield the corresponding diastereomeric complexes with a very high diastereocontrol …”

Synthesis of Nβ-Substituted α,β-Diamino Acids via Stereoselective N-Michael Additions to a Chiral Bicyclic Dehydroalanine

“…This scaffold appears in many natural products, , such as some neurotoxins (e.g., β- N -methylamino- l -alanine, BMAA) or peptidic antibiotics (e.g., duramycin), and has also been used for the synthesis of pharmaceutical compounds. − DAP is a biosynthetic precursor of numerous antibiotics and a siderophore produced by Staphylococcus aureus . Many synthetic approaches have been developed to obtain both DAP enantiomers in a stereoselective manner. − Other important N β -substituted α,β-diamino acids are some analogous of histidine, such as β-(1-pyrazolyl)­alanine or β-(1-triazolyl)­alanine, that involve the substitution of imidazole ring by pyrazole or triazole, respectively, and have been used for diabetes treatment. − These compounds have been accessed by N -nucleophilic displacement of β-haloalanine derivatives, by ring-opening of aziridines, lactones or cyclic sulfamidates, or by chemoenzymatic synthesis using N -Michael addition on dehydroalanines (Dha) . On the other hand, 1-isohistidine is another analog also bearing an imidazole ring but with a different substitution pattern.…”