Threonine aldolases resolution

Scheme 5.49. Resolution of fi-hydroxy-a-amino acids, using threonine aldolase from Strepto-myces amakusaensis.

Threonine aldolases have been also successfully applied in the resolution of racemates of (3-hydroxyamino acids. An interesting example is the use of a D-threonine aldolase from Alcaligenes xylooxidans to resolve DL-threo- 3-(3,4-methylenedocyphenyl)serine, a synthetic intermediate for parkinsonism dmg (Liu et al. 2000b). 

Liu, J. Q., Odani, M., Dairi, T., Itoh, N., Shimizu, S., and Yamada, H., A new route to l-fhreo-3-[4-(methylthio)phenylserine], a key intermediate for the synthesis of antibiotics Recombinant low-specificity o-threonine aldolase-catalyzed stereospecific resolution. Appl. Microbiol. Biotechnol. 1999, 51 (5), 586-591. 

Aryl analogs of threonine 94 (Fig. 32) are of interest for their occurrence as constituents of a number of antibiotics (e.g., vancomycin). Because of often unfavorable equilibrium constants [43], synthetic reactions usually lead to stereoisomer mixtures due to thermodynamic control [152,153]. Resolution of diastereomeric material (93/94) by retroaldolization under kinetic control is more successful, as has been demonstrated by the preparation of enantiopure p-substituted (2i ,35)-phenylserines 94 [154] and (2R,3R)-3-hetarylserines [155] using a threonine aldolase from Streptomyces amakusaensis that is selective for aromatic threo substrates. 

The L-threonine (EC 4.1.2.5), D-threonine (EC 4.1.2.-) or L-allothreonine aldolases (EC 4.1.2.6 synonymous to S1IMT) can be used for resolution of racemic (allo)threonine mixtures by highly selective cleavage of the unwanted isomers42, but can also efficiently direct the anabolic pathways. The substrate spectrum includes propanal, butanal and dodecanal43. 

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