Asymmetric synthesis of new β-heterocyclic (S)-α-aminopropionic acids

The asymmetric synthesis of novel non-proteinogenic β-heterocyclic α-amino acids via the diastereoselective conjugate addition of heterocyclic nucleophiles to the dehydroalanine moiety of chiral Ni(II) complexes has been studied. The complexes were formed from the Schiff base of dehydroalanine using (S)-2-N-(N-benzylprolyl)aminobenzophenone as a chiral auxiliary. After decomposition of the complexes, the α-amino acids were isolated with 30–99% ee.

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(S)-2-Amino-3-(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-yl) propionic acidC9H14N4O4[α]D20=-13.5 (c 0.2, 6M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (S)

(R)-2-Amino-3-(3-ethoxycarbonyl)-6-morpholino-4-phenylpyridin-2-ylthio)propionic acidC21H25S1O5N3[α]D20=+16.5 (c 0.46, 6M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (R):

(R)-2-Amino-3-(4-cyano-1-morpholino-5,6,7,8-tetrahydroisoquinolin-3-ylthio)propionic acidC17H22N4O3S[α]D20=+20.7 (c 0.27, 6M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (R)

(S)-2-Amino-(3-butyl-4-propyl-5-thio-1,2,4-triazol-1-yl)propionic acidC12H22N4O2S[α]D20=-10.4 (c 0.5, 4.9M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (S)

(S)-2-Amino-3-(3-benzyl-4-allyl-5-thio-1,2,4-triazol-1-yl)propionic acidC15H18O2N4S[α]D20=-4.2 (c 1.0, 6M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (S)

(S)-2-Amino-3-(3-butyl-4-(2-methallyl)-5-thio-1,2,4-triazol-1-yl)propionic acidC13H22N4O2S[α]D20=-2.2 (c 0.5, 6M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (S)

(S)-2-Amino-3-(3-pyridine)-4-allyl-5-thio-1,2,4-triazol-1-yl)propionic acidC13H15N5O2S[α]D20=+4.5 (c 1.0, 4.9M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (S)

(S)-2-Amino-3-(4-pyridine)-4-allyl-5-thio-1,2,4-triazol-1-yl)propionic acidC13H15N5O2S[α]D20=+9.4 (c 1.0, 4.9M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (S)

(S)-2-Amino-3-(4-benzylpiperazin-1-yl)propionic acidC14H21N3O2[α]D20=+21.5 (c 0.16, 6M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (S)

(S)-2-Amino-3-(4-bromobenzylpiperazin-1-yl)propionic acidC14H20N3O2Br[α]D20=+23.9 (c 0.26, 6M HCI)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (S)

(S)-2-Amino-3-(2-fluorobenzylpiperazin-1-yl)propionic acidC14H20N3O2F[α]D20=+24.5 (c 0.20, 6M HCl)Source of chirality: (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamideAbsolute configuration: l or (S)