L-allo-Threonine

Extension of this strategy enables syntheses of both protected D-threonine and L-allo-threonine, in which reagent-controlled stereoselective epoxidation of a common intermediate is the key step (Scheme 4.8).53... 

A different synthetic route converted alanine to the diasteromcric mixture of oxazoIidin-2-ones, S.lla and S.llb. After separation of these diastereomers, oxidative cleavage of the alkene moiety in S.IIa (with RuCla and NaI04) led to S.12a and basic hydrolysis gave D-isothreonine S.ISa). L-allo-Threonine (S.J3b) was formed in a similar manner from diastereomer 5,1 Ib, via 5.12b. Note that a variety of amino acids were prepared from alanine. These include both 2-amino, 3-amino, and 4-amino acid derivatives. 

Model reactions of this type have been studied in which the catalyst is pyridoxal plus a metal. The enzymatic reactions all appear to use pyridoxal phosphate as a cofactor, and in the case of a bacterial system, Mn" is also required. A major difference between the enzymatic and the model reactions is the requirement for a folic acid cofactor in the former. The formation of glycine and acetaldehyde from L-threonine and L-allo-threonine has been described by Lin and Greenberg. Their partially purified enzyme, threonine aldolase, was not shown to require any cofactors, and the reaction was not reversed. This is in contrast to the results of nonenzymatic experiments in which pyridoxal and a metal catalyze the reversible cleavage of threonine. 

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. 

L-Threonine [72-19-5] M 119.1, m 251-253°, [a]] -28.4° (H20). Likely impurities are allo-threonine and glycine. Crystd from water by adding 4 volumes of EtOH. Dried and stored in a desiccator. 

A. Golfbiowski and J. Jurczak, The cyclocondensation reaction of l-benzoyloxy-2-fert-butyldimethylsilyloxy-4-methoxy-1,3-butadiene with N.O-protected D-threoninals and D-allo-threoninals. Tetrahedron 47 1045 (1991). 

The stereochemistry of the N-methyl-alanine residue connected to the end of the 3-hydroxy-2,4,6-trimethylheptanoic acid moiety as well as of the allo-threonin placed between the L-methylglutamine and L-threonin residues have been revised to the correct actual stereostructure of callipeltin A (57) [104]. Two additional members of this class, named callipeltins D and E, have been isolated from... 

W. Stbcklein and H.-C. Schmidt, Evidence for L-threonine cleavage and allo-threonine formation by different enzymes from Ciostridium pasteurianium Threonine aldolase and serine hydroxymethyltransferase, Biodiem. ]., 232 621 (1985). 

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). 

Isoleucine, threonine, 4-hydroxyproline and 3-hydroxyproline also have an asymmetric carbon atom in the side chain (two chiral centres in total). They can therefore occur in four stereoisomeric forms (this number is equal to 2 = 2 = 4, where = number of asymmetric carbon atoms) known as l-, d-, L-allo- and d-allo- according to the configuration of the carbon carrying the amino group. The unique RIS system is not widely used in biochemistry. The stereoisomers of isoleudne are thus called L-isoleucine or (2S,3S)-isoleucine (2-4), D-isoleucine or (2R,3R)-isoleucine (2-77), L-a//o-isoleudne or (2S,3R)-isoleudne (2-78) and D-fl//o-isoleucine or (2fi,3S)-isoleucine (2-79). Proteins contain only L-isoleudne. The product of enzymatic or thermal isomerisation of L-isoleucine is D-oZZo-isoleudne. Likewise, proteins contain L-threonine or (2S,3R)-threonine (2-4) and L-4-hydroxyproline or (2S,4S)-4-hydroxyprohne (2-6). Cystine (as well as lanthionine, see Sedion 2.5.1.3.4) contains two identical asymmetric carbons in the molecule and, therefore, only exists in three different isomers. Proteins contain just L-cystine (2-4), its isomer is D-cystine (2-80) and the mesoform meso-cystine (2-81) is a symmetrical molecule. 

Conventional processing of food raw materials, as well as culinary methods used during food preparation, does not usually cause a significant isomerisation (racemisation) of L-amino acids (Table 2.25) (with the exception of aspartic acid), l-Aspartic acid and L-serine undergo racemisation relatively easily. L-lsoleucine (isomerises to D-flHo-isoleucine), L-prohne, L-threonine (isomerises to D-allo-threonine) and L-vahne yield smaller amounts of o-isomers. Free amino acids are roughly ten times more stable than amino acids bound in proteins. An extensive racemisation of amino acids does however occur, even at relatively low temperatures, in alkaline media used to inactivate enzymes, microorganisms, microbial... 

Different ThrAs possessing variable stereoselectivities are described in the literature (c/review ). The L-threonine aldolases can be divided into three different subgroups, the L-ThrA (catalyzing the formation of L-threonine), the L-allo-ThiA, and the l-1ow specific enzymes (L-low-ThrA, catalyzing the formation of both L-Thr and L-allo-Thr), whereas only low specific D-aldolase (o-ThrA, catalyzing... 

The preparation of protected derivatives of D-allo- and L-fl//o-threonine by enzymatic hydrolysis of 5(47/)-oxazolones using hog kidney acylase has also been described. This methodology has been extended to a wide variety of amino acids and, at present, constitutes a general procedure to prepare non-quaternary... 

Almost all actinomycins have the same chromophore, a planar phenoxazinone dicarboxylic acid called actinociiL In dactinomycin, the structure of which is shown in Figure 12, the two pendent pentapeptide lactones are identical, but in other actinomycins these lactones may be different. In other actinomycins the first amino acid, amide linked with actinocin, is usually L-threonine, as in dactinomycin the second position is sometimes D-allo-isoleucine instead of D-valine the third position may be sarcosine or oxoproline the fourth position is sarcosine and the fifth position is sometimes iV-methyl isoleucine instead of N-methylvaline. The lactone ring is always present. 

Threonine (Thr, T), i-threo-a-amino-/3-h.yd-roxybutyric acid, H3C-CH(OH)-CH-(NH2)-COOH, C4H9NO3, Mr 119.12 Da, a pro-teinogenic amino acid with two asymmetric C atoms existing in a threo- and an allo-form from which the L-tkreo-form occurs in proteins. 

Intramolecular nucleophilic substitution by an active methylene linked to the nitrogen atom of a-substituted carboxamides was first utilized in azetidinone synthesis by Sheehan and Bose in 1950 [27]. When 3-hydroxyethylazetidinones became an important research target, it was realized that L-threonine or D-allo-treonine, easily converted to bromohydrins 57,61 or to epoxyacid 64, are by this method one of the most convenient natural chiral source for penem and carbapenem synthesis. Shiozaki et al. [28] at Sankyo s laid down the fundaments of the threonine route . Early works from D-a//o-threonine-derived 2R-bromo-3R-hydroxybutyric acid 57 were run using malonate anions as the nucleophilic moiety, as shown in amide 58, which in presence of DBN cyclized to azetidinone 59a with complete inversion of configuration [28a, c]. 

Scheme 5.27. Synthesis of benzoxazepinesfrom L-threonine and allo-L-threonine.

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