L-Allothreonine

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. 

C( H, 02 99-93-4) see Bamethan Bufexamac Paracetamol Pifoxime Salbutamol 4-hydroxy-L-allothreonine monosodium salt (C4H,NNa04 117095-55-3) see Carumonam 4 -hydroxy-2-aminoacetophenone (CSH9NO2 77369-38-1) see Octopamine... 

In the enzymatic part of the process, a one-pot conversion was achieved by using Candida lipase (Lip) to hydrolyze the ester and then LeuDH to catalyze the reductive amination (with or without N labeling). In this case, the coenzyme recycling was accomplished by adding FDH and formate. The same group used a similar enzymatic strategy to prepare labeled L-threonine and L-allothreonine starting from the a-keto methyl ester. ... 

A similar stereochemical question as in the /8-replacement reactions can be asked in the a, /8-eliminations where the group X is replaced by a hydrogen, i.e., is the proton added at C-/8 of the PLP-aminoacrylate on the same face from which X departed or on the opposite face This question has been answered for a number of enzymes which generate either a-ketobutyrate or pyruvate as the keto acid product. Crout and coworkers [119,120] determined the steric course of proton addition in the a,/8-elimination of L-threonine by biosynthetic L-threonine dehydratase and of D-threonine by an inducible D-threonine dehydratase, both in Serratia marcescens. Either substrate, deuterated at C-3, was converted in vivo into isoleucine, which was compared by proton NMR to a sample prepared from (3S)-2-amino[3-2H]butyric acid. With both enzymes the hydroxyl group at C-3 was replaced by a proton in a retention mode. Although this has not been established with certainty, it is likely that both enzymes, like other bacterial threonine dehydratases [121], contain PLP as cofactor. Sheep liver L-threonine dehydratase, on the other hand, is not a PLP enzyme but contains an a-ketobutyrate moiety at the active site [122], It replaces the hydroxyl group of L-threonine with H in a retention mode, but that of L-allothreonine in an inversion mode [123]. Snell and coworkers [124] established that the replacement of OH by H in the a, /8-elimination of D-threonine catalyzed by the PLP-containing D-serine dehydratase from E. coli also proceeds in a retention mode. They... 

A stereospecific total synthesis of the antibiotic sibirosamine was carried out using this methodology. In the first step, addition of methylmagnesium iodide to N-(phenylsulfonyl)-L-allothreonine afforded the a-amino methyl ketone in modest yield. This reaction afforded a diminished yield compared with N-(phenylsulfonyl)-L-threonine for some unexplained reason. A clever use of Ae L-amino acid serine sdlows for a straightforward preparation of o-amino acids such as o-dopa as is shown in Scheme 15. ... 

The CHF and CF2 groups are superior to CH2 as isosteres of oxygen and this has led to extensive interest in their chemistry. The a-difluorophosphonate analogues of the phosphates of L-serine (219), L-threonine (220), and L-allothreonine (221) have been prepared by highly enantioselective reactions of difluoromethylpho-sphonate carbanion with chiral esters. Lipase PS catalysed acetylation of prochiral 1,3-propandiol alkylphosphonates 222 is reported to be highly enantioselective and the resulting monoacetate enantiomers 223 have been used to synthesise a series of (o-phosphono-a-amino acids, 224 and 225.Other routes to 225, one of... 

For the structures of natural L-threonine ((2S,3R)-threonine) and L-allothreonine ((2S,3S)-threonine), replace the side-chain ethyl group (C2H5) in isoleucine and alloisoleucine by OH. 

When hydroxyaldehydes are employed as L-Thr aldolase substrates, complex product mixtures result. Protection of the hydroxyl groups prevents this, and allowes the preparation of C4-protected L-threonine and L-allothreonine derivatives. Acceptor aldehydes with an oxygen functionality at the a-position gave high erythro/threo... 

The enzyme threonine dehydratase (EC 4.2.1.16) has been shown to dehydrate both L-threonine 128a and L-allothreonine 129 in to yield (3R)-[3- H,]-a-ketobutyrate 124 (131) (Scheme 40), the configuration of which was proven by conversion to (2R)-[2- H,]propionate and comparison of the ORD with that of an authentic sample. This implies either that the bound substrates 128a and 129 dehydrate with different stereochemistries and protonate from the same side or that they dehydrate in identical fashion and protonate from different sides. Threonine dehydratase has an important role in the biosynthesis of valine, as we shall see in Section VIII. 

C-N.m.r. Chemical-shift Data for the Anomeric-Carbon Atom (C-1) and the Threonine Methyl Carbon Atom (O) of Diastereomeric a- and/S o-Calactopyranosyl-L-threonine, -D-threonine, -L-allothreonine, and -D-allothreonine ... 

For example, the configuration of L-threonine is 2S, 3R and that of its enatiomer, d-threonine is 2R, 3S. L-Allothreonine with 2S, 3S configuration is its diastereomer. It is noted that a helical chain is chiral, having right-handed (clockwise) and left-handed (counterclockwise) chirality. 

Yasui et al. (1965 Yasui, 1965) studied the CD spectra of copper-amino acid complexes in more detail and showed that copper complexes with l-amino acids in water exhibit four Cotton effects in the region of the d-d absorption band positive at 830 and 730 nm and negative at 635 and 565 nm. The CD curves of the complexes of proline, hydroxyproline, and histidine are considerably different from those of other amino acid complexes for which the main CD band at ca. 630 nm shows the opposite positive Cotton effect. It was suggested that the vicinal effect of the asymmetric a-carbon atom is stronger than that of the asymmetric j -carbon atom (L-threonine and L-allothreonine) and thus determines the sign of the Cotton effects. 

Among the amino acids, threonine, hydroxylysine, cystine, isoleucine, the two hydroxyprolines, and others possess two optically active centers. Therefore, the synthetic compounds are mixtures of four diastereoisomers the l- and d- forms, and the L-allo- and D-allo- forms, respectively. For example, threonine can have these four forms L-threonine (XLI), D-threonine (XLII), L-allothreonine (XLIII), and D-allothreonine (XLIV). 

The N-phenylsulphonyl derivative (44) of sibirosamine (c.f. Scheme 10) has been synthesized from the L-allothreonine derivative (45) as shown in Scheme 14, involving stereospecific addition of... 

C4H9NO3, L(S)-Threonine, 13, 488 40B, 434 C HjNOa, L-Allothreonine, 41B, 525 CftHgNOa, L-Threonine - L-allothreonine, 41B, 526 C4H9NO3S, (+)-S-Methyl-L-cysteine sulfoxide, 27, 765 CftH9NOsS, DL Homocysteic acid, 43B, 589... 

The best enzyme source is sheep liver. Only the L-forms of threonine and allothreonine are susceptible to attack. L-Allothreonine is cleaved twenty to twenty-five times as rapidly as L-threonine by crude liver extracts. The evidence that two separate enzymes are involved is as follows ... 

Both threonine aldolases were demonstrated to be pyridoxal phosphate-dependent and to be sulfhydryl enzymes. Michaelis constants were calculated to have the values of 69 X 10 M for L-threonine and 4.25 X 10 M for L-allothreonine. 

Synthesis of the threonines from acetaldehyde and glycine can be catalyzed by the enzyme preparations as well as the decomposition of the amino acids 43,44)- Karasek and Greenberg 44) determined that the equilibrium constant for the reaction (allothreonine)/(acetaldehyde) (glycine) was approximately 56. It is difficult to understand the occurrence of an enzjmne specific for L-allothreonine with higher activity than the enzyme that decomposes L-threonine since the former amino acid has not been discovered to exist in natural materials. 

Threonine (a-amino-d-hydroxybutyric acid) is the next higher homolog to serine. Its name points to the relationship with the sugar threose. Threonine has two asymmetric centers (cf. Chapt. 1-4) manifested by four stereoisomeric forms of which two are always mirror images of the other two namely d- and L-threonine and D- and L-allothreonine. Threonine was discovered in an interesting manner it was identified as a necessary supplementary factor of a synthetic diet mixture (Rose 1935) and thus became the first amino acid to be recognized as indispensable. 

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