The Synthesis of DL-Threonine. II. Interconversion of DL-Threonine and DL-Allothreonine

Pfister, Karl; Robinson, Charles Alexander; Shabica, Anthony C.; Tishler, Max

doi:10.1021/ja01171a094

Cited by 40 publications

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“…Inversion of configuration at the P-position of P-hydroxy-a-amino acids can usually be accomplished via the oxazoline (25,26). However, attempts to prepare an oxazoline by treating N-benzoyl-DL-erythro-P-hydroxyisoleucine methyl ester with thionyl chloride under the appropriate conditions gave back the starting material.…”

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confidence: 99%

Synthesis of DL-threo- and DL-erythro-β-hydroxyisoleucine

Dobson¹,

Vining²

1968

Can. J. Chem.

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DL-threo-and DL-erythro-B-Hydroxyisoleucine were prepared from cis-and trans-3-methylpent-2-enoic acids, respectively. The configuration of the erytl~ro isomer was established from its synthesis by two independent routes. The diastereoisomers, and those of other B-hydroxy amino acids, can be distinguished by examination of their proton magnetic resonance spectra. ICanadian Journal of Chemistry, 46, 3007 (1968) An investigation of the biosynthesis of aspergillic acid in cultures of Aspergillus Javus, which showed that this pyrazine derivative is , derived from leucine and isoleucine (I), led us to I conjecture that hydroxyaspergillic acid might be 1 formed similarly from leucine and P-hydroxy-I isoleucine. Although subsequent work proved 1 this to be incorrect (2), preliminary feeding I trials with a mixture of the DL-threo and erythro I isomers of P-l~ydroxyisoleucine had shown strong inhibition of aspergillic acid production 1 without noticeable effect on the growth of A.Javus. In order to examine this effect further each isomeric amino acid has been prepared in a pure form. These compounds may also be of value in elucidating the biosynthesis of two other plant metabolites, cleomin (3) and linamarin (4) which contain elements of the P-hydroxyisoleucine skeleton.Attempted synthesis of P-hydroxyisoleucine from methyl ethyl ketone and glycine using the general route for P-hydroxy a-amino acids described by Otani and Winitz (5) was unsuccessful. However the amino acid was conveniently prepared from methyl ethyl ketone and ethyl dichloroacetate via the glycidic ester. Alkaline hydrolysis (6) yielded the acid which, after reaction with benzylamine followed by hydrogenolysis as described by Liwschitz et al. (7) gave P-hydroxyisoleucine in an overall yield of trans glycidic esters (8). These were detected by gas-liquid chromatography (g.1.c.) but could not be separated on a preparative scale. Ailalysis by ion exchange chromatography of the P-hydroxyisoleucine obtained from this procedure showed the expected mixture of diastereoisomers, but attempts to effect the separation of milligram quantities by ion exchange chromatography with larger columns were unsatisfactory. No useful separations were obtained by paper chromatography, or by fractional crystallization.As an alternative route to the synthesis of each of the P-hydroxyisoleucines a procedure used by West et al. (9) for the preparation of threonine and allothreonine was explored. 3-Methylpent-2-enoic acid, obtained as described by Kon and Linstead (lo), was a liquid from which a crystalline product, m.p. 46", was obtained by fractional distillation. This compound, previously described by several workers (1 1, 12), was found from g.1.c. and spectral evidence, to represent one of the isomeric a,P-unsaturated acids. The second isomer was separated in a pure form by preparative g.1.c. and obtained as a crystalline solid, m.p. 35.5". Structures are assigned to these compounds on the basis of their nilclear magnetic resonance (n.m.r.) spectra (Table I). Jackman and W...

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confidence: 99%

Synthesis of DL-threo- and DL-erythro-β-hydroxyisoleucine

Dobson¹,

Vining²

1968

Can. J. Chem.

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“…The intermediacy of 2 ~ was, however, de~i~onstrated by t.l.c., and it was confirmed that under the hydrolysis conditions (0.8 N hydrochloric acid in aqueous ethanol) isomerization of 2 to 3 was rapid and efficient. The same zster 3 could also be obtained from the trans-isomer 5 of the alcohol 2, though not under such mild conditions, the use of thionyl chloride o r concentrated sulfuric acid being necessary, in which case the yield was quantitative. …”

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confidence: 89%

“…The conversion of 5 into 3 is in fact an example of a well established reaction type in which an a-acylamino alcohol is transformed by acidic reagents (most frequently thionyl chloride) into a derivative of the amino alcohol with inversion at the carbinol carbon (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). The key step is the formation of an oxazolinium cation by S,2 attack of the acylamino oxygen.'…”

Section: Cophmentioning

confidence: 99%

“…These have been isolated as the free bases, (e.g. 6 from trans-2-benzoylaminocyclohexanol) which are usually stable, or as their salts (3)(4)(5)(7)(8)(9)(10). Hydrolysis of the oxazolines by acids gives the cis-2-acyloxycycloalkylamines (C-N cleavage, overall N + 0 migration) (2,4, 7, 8, lo), or, if prolonged, the cis-alcohols themselves (3, 5-8, lo), while hydrolysis by basic reagents appears to give cis-2-acylaminocycloalkanoIs (C-0 cleavage) (8,9).…”

Section: Cophmentioning

confidence: 99%

“…spectrum were followed when first one and then a second equivalent of tosyl chloride was added to 5 (0.7 M) in chloroform-d containing 2.5 equiv of pyridine.5 The broad peak for the tert-hydrogens of 5 at 5.5 z slowly diminished while absorptions grew at lower field, including ones near 4.0 and 4.6 z; at the same time the n;ethyl peak of N-tosylpyridiniurn chloride at 7.60 r6 was replaced by one at 7.73. The spectrum remained unchanged after about 10 h when the peak at 5.5 z was about half its original area, and the peak at 7.60 z had almost disappeared.…”

Section: Cophmentioning

confidence: 99%

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Substituent Interactions in Di- and Tri-acyl Derivatives of cis- and trans- 2-Hydrazinocyclopentanol

Campbell¹,

Mackay²

1973

Can. J. Chem.

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The action of thionyl chloride followed by an alkaline work-up quantitatively isomerizes trans-1,2-dibenzoyl-1-(2-h~droxylcyclopentyl)hydrazine (5) to cis-2-benzoyl-I-(2-benzoyloxycyclopentyl)hydrazine (3). One equivalent of tosyl chloride in pyridine converts 5 to an intermediate which can be hydrolyzed to a mixture of 3 and 5 or can be transformed to the N-tosyl derivative 13 by tosylation and then hydrolysis. Oxazolidine structures are s~~ggested as intermediates for these reactions.The alcohol 2 can also be isomerized to 3, using 0.8 N aqueous ethanolic hydrochloric acid, to which 5 is inert. The ester 3 is again the major product in the hydrolysis by this acid mixture of the cis-tribenzoyl derivative 17, the cis-N,-p-anisoyl derivative 21a and the cis-N,-acetyl derivative 216, the amide group being cleaved much more rapidly than the ester, especially in the case of 216. A mechanism involving ester participation by way of an oxazolidinium cation is proposed for these amide hydrolyses, and this is supported by tracer studies.The trntu-esters 24n and b hydrolyze mainly at the ester group with retention of configuration. Polynlorphism is a common phenomenon among thc title compounds.L'action du chlor~lre de thionyle suivie d'un traitement alcalin isoniCrise quantitativement le traiudibenzoyl-1,2 (hydroxyl-2 cyclopenty1)-l hydrazine (5) en cis benzoyl-2 (benzoyloxy-2 cyclopenty1)-l hydrazine (3). Un equivalent de chlorure de tosyle dans la pyridine transforme 5 en un intermediaire qui peut Ctre hydrolyse en un melange d e 3 et 5 ou convertit en derive N-tosyle 1 3 par tosylation puis hydrolyse. Les structures oxazolidines ont ete suggCrees comme intermediaires reactionnels. L'isomCrisation de I'alcool2 en 3 est Bgalement possible en presence d'une solution aqueuse Cthanolique d'acide chlorhydrique 0.8 N pour laquelle 5 est inerte. L'ester 3 reste encore le produit majoritaire dans I'hydrolyse par ce melange acide, du derive cir-tribenzoyle 17, du derive cis N,-p-anisoyle 21a et du dCriv6 cis-N,-acetyle 21b, le groupe amide etant dive beaucoup plus rapidenlent que I'ester specialement dans le cas de 21b. Un mecanisme avec participation de I'ester par un cation oxazolidinium a CtC propose pour les hydrolyses de ces amides; ce mecanisme a ete confirm6 par les Ctudes par traceur.Les esters tratrs 24a et 6 s'hydrolysent principalement sur le groupe ester avec retention de configuration. Le polymorphisme est un phenomene conimun parlni les composes de cette etude.[Traduit par le journal]Can. J . Chcn., 51. 1587 (1973) In earlier work (1) we used as partial proof of the structure of 1, the dihydro derivative of the thermal rearrangement product of cyclopentadiene and azodibenzoyl, its ready hydrolysis by acid to cis-1,2-dibenzoyl-1-(2-hydroxycyclopenty1)hydrazine (2). The alcohol 2 was not itself isolated, but'rather its isomer, the ester 3, and the further hydrolysis product 4. The intermediacy of 2 ~ was, however, de~i~onstrated by t.l.c., and it was confirmed that under the hydrolysis conditions (0.8 N hydrochlor...

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dl‐Threonine

Carter¹,

West²

2003

Organic Syntheses

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dl ‐Threonine intermediate: α‐ Bromo‐β‐methoxy‐n‐butyric acid. intermediate: formyl‐ dl ‐O‐methylthreonine product: dl ‐threonine intermediate: Formyl‐ dl ‐O‐methylallothreonine

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The Synthesis of DL-Threonine. II. Interconversion of DL-Threonine and DL-Allothreonine

Cited by 40 publications

References 0 publications

Synthesis of DL-threo- and DL-erythro-β-hydroxyisoleucine

Synthesis of DL-threo- and DL-erythro-β-hydroxyisoleucine

Substituent Interactions in Di- and Tri-acyl Derivatives of cis- and trans- 2-Hydrazinocyclopentanol

dl‐Threonine

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