Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
  • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
  • C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters

Definitions

• the present invention relates to a new process for obtaining amino acids and the esters thus obtained.
• the esterification of the carboxylic function in ⁇ of the amino function is an effective blocking mode to allow condensation reactions, either on the adjacent amino function, or on a function present on the carbon chain of the amino acid.
• This is how the chain can carry a hydroxyl as in the case of serine or ⁇ acid - amino hydroxy butyric - an amino function like lysine, another carboxylic function like glutamic acid or aspartic acid or a guanidine function such as arginine. It is therefore necessary in many cases, to start a peptide synthesis to block one of the reactive functions to allow condensations on another reactive function of the molecule.
• esterification of amino acids which constitutes one of the blocking modes, often poses difficult problems due to the proximity of an amino function. Avoid using an alkylating or aralkylating agent which could also react with the amino function. Very acidic agents or very acidic conditions must also be avoided because the protonation of the amino function deactivates the carboxylic function. In addition, esterification in an acid medium gives rise to the formation of water and the reaction tends towards an equilibrium.
• the method according to the invention aims to solve a large number of these problems. It makes it possible to obtain an amino acid ester with an almost quantitative yield and to isolate it in pure form in a very easy manner. It makes it possible to be able to optionally recover the unreacted amino acid, in the form insoluble in the reaction medium.
• the method consists in subjecting an amino acid to the action of an alkanol in the presence of an equimolecular amount of an alkyl sulfate and in isolating the ester thus formed in the form of acid alkyl sulfate which is converted into an oase and then reconverted into salt, if desired.
• the process according to the invention can also be defined by the following methods which are currently preferred: 1 /
• the alkanol is preferably an aliphatic alcohol of low molecular weight.
• the alkyl sulfate is preferably a lower alkyl sulfate whose alkyl radical is the same as that of the alkanol.
• reaction is carried out using equimolecular proportions of amino acid and alkyl sulfate.
• the amino ester alkyl sulfate is converted into the base by addition of an alkaline agent.
• the amino ester can be converted into a salt by adding a mineral or organic acid in solution in an anhydrous organic solvent.
• esters according to the invention are known intermediates, used for peptide synthesis such as for example the synthesis of oxytocin, TRH or aspartame.
• the following examples illustrate the invention without, however, limiting it.
• the crystals are separated by filtration, washed with acetone and dried under vacuum or in a ventilated oven at 45 ° - 191.92 g of methyl phenylalaninate sulfate (white crystalline product) are thus obtained.
• the mixture is concentrated to half volume and the crystallization is initiated by scraping at ordinary temperature.
• the crystalline mixture is left to stand overnight in a cooler.
• the crystals are separated and washed with cold ethanol and then dried.
• the suspension is brought to reflux for 4 hours and then allowed to cool to ambient temperature.
• the mixture After homogenization of the mixture, the mixture is heated to 80 ° C. for 6 hours then allowed to cool and the excess reagent is removed by vacuum distillation. The residual mixture is taken up by the minimum quantity of hot dioxane from which it recrystallizes by cooling. After a few hours' rest, the terbutyl sulphate of terbutyl tryptophanate is separated by filtration. The crystals are separated, wrung thoroughly, then dried at constant weight under vacuum. They are redissolved in 300 ml of methylene chloride and agitated against the current with aqueous sodium hydroxide. The organic phase is separated, washed with water until the washings are neutral, dried over sodium sulfate, filtered and then evaporated to dryness.
• the crystalline residue is taken up in isopropyl ether.
• the solution is diluted with an equal volume of cyclohexane.
• Terbutyl tryptophanate gradually precipitates. It is separated by filtration, wrung, rinsed with cyclohexane and dried.
• the residue weighing 291 g consists of pure terbutyl tryptophanate.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Indole Compounds (AREA)
• Peptides Or Proteins (AREA)

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Publications (1)

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• 1981
  • 1981-03-11 FR FR8104816A patent/FR2501677A1/fr active Granted
• 1982
  • 1982-03-11 JP JP57500844A patent/JPS58500442A/ja active Granted
  • 1982-03-11 EP EP19820900808 patent/EP0074968A1/fr not_active Withdrawn
  • 1982-03-11 WO PCT/FR1982/000043 patent/WO1982003074A1/fr not_active Ceased

Non-Patent Citations (1)

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