Preparation of Optically Active Allothreonine via Optical Resolution by Replacing Crystallization

Tadashi Shiraiwa, Keiji Fukuda, Motoki Kubo
2002 Chemical and pharmaceutical bulletin  
D-and L-Allothreonine [D-and L-aThr; (2R,3R)-and (2S,3S)-2-amino-3-hydroxybutanoic acid] are useful as chiral reagents in asymmetric syntheses. 1) However, D-and L-aThr, non-proteinogenic a-amino acids, are difficult to produce commercially in large quantities. Therefore, synthetic DL-aThr 2-4) has been subjected to optical resolution by separating the diastereoisomeric salts of DL-aThr derivatives to obtain the enantiomers. 5,6) In our previous paper, 7) DL-aThr was found to exist as a
more » ... rate and to be optically resolved by preferential crystallization and replacing crystallization of DL-aThr. The optical resolution by replacing crystallization is a procedure for obtaining an enantiomer from a conglomerate, and is achieved by allowing an optically active co-solute to coexist in a racemic supersaturated solution. 8) DL-aThr was optically resolved using 4-hydroxy-L-proline (L-Hyp) as the optically active cosolute, and D-aThr was allowed to preferentially crystallize from a supersaturated solution of DL-aThr. 7) Although L-aThr will be preferentially crystallized from the racemic solution in the presence of D-Hyp, L-Hyp is expensive and D-Hyp is not commercially available. Therefore, we selected D-and L-Ala, which are commercially available and are the most inexpensive optically active a-amino acids, as the optically active cosolutes in optical resolution by replacing crystallization of DL-aThr (Chart 1). Optical resolution by replacing crystallization is based on different interactions between enantiomers and the optically active co-solute. Therefore, the solubilities (mole fractions) of D-, L-, and DL-aThr were first measured in the presence of L-Ala (16.0 mmol) in 100 cm 3 of water at 10°C; these values are summarized in Table 1 , together with the solubilities 7) in the absence of L-Ala. When L-Ala was present in aqueous solutions of D-, L-, and DL-aThr, D-aThr was less soluble than L-aThr. In addition, D-, L-, and DL-aThr were each less soluble in the presence of L-An attempt was made to use a simple procedure to obtain D-and L-allothreonine (D-and L-aThr), which are non-proteinogenic a a-amino acids and are useful as chiral reagents in asymmetric syntheses. DL-aThr that exists as a conglomerate was optically resolved by replacing crystallization with L-alanine (L-Ala) as an optically active co-solute. D-aThr was preferentially crystallized from an aqueous solution of DL-aThr in the presence of L-Ala, as was L-aThr in the presence of D-Ala. Furthermore, a diasteroisomeric mixture of D-aThr and L-threonine (L-Thr) and one of L-aThr and D-Thr were prepared, respectively, by epimerization of L-and D-Thr using salicylaldehyde as the catalyst in acetic acid. Based on the result of the replacing crystallization, D-and L-aThr were separated from aqueous solutions of the diastereoisomeric mixtures in the presence of L-and D-Ala. The partially resolved D-and L-aThr were recrystallized from water to yield the corresponding enantiomers in optically pure forms. Reagents: (a) i) N-Bromosuccinimide, H 2 O, ii) concentrated aqueous ammonia; (b) L-Ala as an optically active co-solute; (c) D-Ala as an optically active co-solute; (d) salicylaldehyde, acetic acid, 80°C.
doi:10.1248/cpb.50.287 pmid:11848226 fatcat:5cqvprqcbfgz5npsmhrv3pwdjy