Threonine synthetic

In the case of copper(II) complexes, the reaction with acetaldehyde is believed to proceed by the steps shown in Scheme 38. The bis(oxazolidine)copper(II) complex (148 R = Me) has been characterized by X-ray analysis.486 Treatment of this complex with H2S in acid solution gives threonine. Synthetic procedures have been developed giving threonine in 95% yields.483... 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Reaction of Bisglycinatocopper(II). Bisglycinatocopper(II) [13479-54-4] condenses with ahphatic aldehydes. Removal of copper from the condensate results in P-hydroxy-a-amino acid. This is a classical synthetic method of DL-threonine, but the formation of i //o-isomer is unavoidable. 

SYNTHETIC N- AND OGLYCOSYL DERIVATIVES OF l-ASPARAGINE, l-SERINE, AND l-THREONINE... 

The physical properties of the synthetic glycosyl derivatives of l-asparagine, L-serine, and L-threonine are reported in Tables I-V. Derivatives characterized otherwise, but without m.p. and optical rotation, have also been included. Whenever more than one reference is given, the physical constants are taken from the references printed in bold letters. The abbreviations used in the m.p. column are as follows foam., foaming dec., decomposing and soft., softening. 

Scheme 1 summarizes our synthetic approach. By protecting the carboxyl groups using a suitable protecting group, the three hydroxy amino acids, serine, threonine and tyrosine were conveniently coupled with Boc-Phe-OH to obtain the corresponding peptides (1-4) in good yields. 

A classical approach to driving the unfavorable equilibrium of an enzymatic process is to couple it to another, irreversible enzymatic process. Griengl and coworkers have applied this concept to asymmetric synthesis of 1,2-amino alcohols with a threonine aldolase [24] (Figure 6.7). While the equilibrium in threonine aldolase reactions typically does not favor the synthetic direction, and the bond formation leads to nearly equal amounts of two diastereomers, coupling the aldolase reaction with a selective tyrosine decarboxylase leads to irreversible formation of aryl amino alcohols in reasonable enantiomeric excess via a dynamic kinetic asymmetric transformation. A one-pot, two-enzyme asymmetric synthesis of amino alcohols, including noradrenaline and octopamine, from readily available starting materials was developed [25]. 

Yeast strains are grown on either standard yeast extract, peptone, glucose media (YPD) (1% (w/v) yeast extract, 2% (w/v) bactopeptone, and 2% (w/v) glucose) and supplemented with the appropriate antibiotic, or in synthetic complete media (SCD media) (0.17% (w/v) yeast nitrogen base. 0.5% (w/v) ammonium sulphate, 2% (w/v) glucose, and supplemented with 20 mg/1 arginine, 100 mg/1 aspartic acid, 100 mg/1 glutamine, 30 mg/1 isoleucine, 30 mg/llysine, 20 mg/1 methionine, 50 mg/1 phenylalanine, 400 mg/lserine, 200 mg/1 threonine, 30 mg/1 tyrosine, and 150 mg/1 valine. When needed, the media was also supplemented with 20 mg/1 adenine, 10 mg/1 leucine, 60 mg/1 histidine, 60 mg/1 tryptophan, and 20 mg/1 uracil). 

The interaction with both synthetic and naturally occurring amino acids has been studied extensively glycine (138, 173, 219-221), a-(173, 219) and /3-alanine (138, 220), sarcosine (219), serine (222), aspartic acid (138, 173, 222-226), asparagine (222), threonine (222), proline (219), hydroxyproline (219), glutamic acid (138, 222-225), glutamine (222), valine (219, 227), norvaline (219), methionine (222, 226), histidine (228, 229), isoleucine (219), leucine (219, 230), norleu-cine (219), lysine (222), arginine (222), histidine methyl ester (228), phenylalanine (138, 222), tyrosine (222), 2-amino-3-(3,4-dihydroxy-phenyl jpropanoic acid (DOPA) (222), tryptophan (222), aminoiso-butyric acid (219), 2-aminobutyric acid (219,231), citrulline (222), and ornithine (222). 

Figure 3.13 (a) Feedback control of a hypothetical pathway. (b) Feedback control of threonine deaminase in the isoleucine synthetic pathway and of aspartate carbamoyltransferase in the cytidine triphosphate synthetic pathway in the bacterium E. coli. 

Figure 8.4. Amino acid sequence of porcine insulin is depicted in (a). Trypsin cleavage sites are also indicated. Trypsin therefore effectively removes the insulin carboxy-terminus B chain octapeptide. The amino acid sequence of human insulin differs from that of porcine insulin by only one amino acid residue. Porcine insulin contains an alanine residue at position 30 of the B-chain, whereas human insulin contains a threonine residue at that position. Insulin exhibiting a human amino acid sequence may thus be synthesized from porcine insulin by treating the latter with tr5q)sin, removal of the C terminus fragments, generated and replacement of this with the synthetic octapeptide shown in (b). Reproduced by permission of John Wiley Sons Ltd from Walsh Headon (1994)...

An alio-threonine analogue was prepared in this way. The Nebraska group has also explored the use of diallyl phosphonates driven by the need to develop mild deprotection methods [77]. Treatment of ketophosphonates with alkoxide base led to the formation of difluoroenolates and thus difluoromethylketones [78]. The lithiophosphate then acts as a synthetic equivalent for the difluoro-methyl anion synthon (Eq. 21). 

S ATP -I- peptide <3> (<3> synthetic [9,13,14] <3> e.g. Leu-Glu-Glu-Ser-Ser-Ser-Ser-Asp-His-Ala-Glu-Arg-Pro-Pro-Gly or Arg-Arg-Arg-Glu-Glu-Glu-Glu-Glu-Ser-Ala-Ala-Ala, role of acidic amino acids in peptide substrates, preference for negatively charged amino acids localized to the N-terminal side of a Ser- or Thr-residue, Ser-containing peptides are 4fold better than Thr-containing [9] <3> /1-ARK 1 and 2 prefer peptide substrates with acidic amino acids N-terminal to a Ser-residue [13] <3> /)-ARK 1 prefers peptides containing acidic residues on the N-terminal side of a serine or threonine, presence of activated receptor enhances peptide phosphorylation [14]) (Reversibility <3> [9,13,14]) [9, 13, 14]... 

Literature data on the carbon skeleton elongation may be classified according to the number of carbon atoms added. Such a classification, although far from being ideal, is useful from the synthetic viewpoint. Scheme 2 illustrates the usefulness of a-amino acids (in particular a-amino-(3-hydroxy acids e.g., serine, threonine, and their homologues) in the synthesis of amino sugars. 

A corresponding ThrA has been detected in a number of strictly anaerobic bacteria, and the enzyme from Clostridium pasteurianum has been purified and shown to be highly selective for L-threonine 150 [457]. A corresponding L-specific catalyst has also been purified and crystallized from cells of the yeast Candida humicola. Very recently, the latter enzyme was reinvestigated for synthetic purposes and found to have a very broad substrate tolerance for the aldehyde acceptor, notably including variously substituted aliphatic and aro-... 

The synthetic applications of these reactions are considered in Section 61.4.15. Reaction of copper(II) glycinate with formaldehyde in aqueous solution at pH 12 gives serine, while reaction with acetaldehyde gives a mixture of threonine and allothreonine (Scheme 35). This reaction has been extended to a variety of aldehydes to obtain longer chain /3-hydroxyamino acids.439... 

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