Synthesis of the four stereoisomeric forms of α,β diaminobutyric acid and some derivatives suitable for peptide synthesis

DOI: 10.1515/bchm2.1973.354.2.689

Source and publish data:

Hoppe-Seyler's Zeitschrift fur Physiologische Chemie p. 689 - 696 (1973)

Update date:2022-08-06

Topics:

Authors:

Atherton

Meienhofer

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Article abstract of DOI:10.1515/bchm2.1973.354.2.689

A synthetic route to the four stereo isomers of α,β diaminobutyric acid (α,β-A₂bu) has been developed. The L threo, D threo, L erythro and D erythro isomers were prepared from the corresponding threonine and allo threonine isomers. N tosylation under Schotten Baumann conditions was followed by esterification with diazomethane and O tosylation in pyridine to give N,O ditosyl threonine methyl ester (IV). Successive treatments with ammonia saturated methanol and 6N HCl afforded, after several recrystallizations from water, N(α) tosyl α,β diaminobutyric acid (V) of the same configuration as the starting threonine along with racemic mixtures. Presumably, the sulfonamide moiety influenced the steric course of the reaction, causing a double inversion of the C(β) asymmetry center via intermediate aziridine formation. Simultaneous α,β elimination produced the accompanying racemic mixtures via 1 tosylaminocrotonic acid methyl ester. Removal of the tosyl group by the action of sodium in liquid ammonia gave α,β diaminobutyric acid (VI). The configurations of the four isomers were established by NMR and ORD spectra and by conversion of N(α) tosyl L threo α,β diaminobutyric acid (L threo V) to N tosyl L threonine (L threo II) through treatment with nitrous acid. The threo and erythro isomers of α,β A₂bu (VI) and N(α) tosyl α,β A₂bu (V) were further characterized by their elution behavior on ion exchange colum chromatography (amino acid analyzer) and by their ninhydrin color constants (C(HW)). The erythro isomers of α,β A₂bu gave higher color constants (20.6) than the threo isomers (5.6 to 5.8). In the case of N(α) tosyl α,β A₂bu, however, the threo isomers produced higher ninhydrin color values (11.3-11.4) than the erythro isomers (1.7 to 1.8). The NMR spectra (in DCl) of N(α) tosyl L threo α,β A₂bu (L threo V) exhibited an H(α)-H(β) coupling constant (6.6 Hz) which is identical with that of the erythro isomers of the free amino acid (α,β A₂bu). Several derivatives of L threo α,β diaminobutyric acid (L threo VI) suitable for use in peptide synthesis were prepared, including N(α) Tos N(β) Boc α,β A₂bu, N(β) Boc α,β A₂bu, N(α) Z N(β) Boc α,β A₂bu, N(α) Z N(β) Boc α,β A₂bu OMe, and N(α) Z α,β A₂bu Ome x HCl.