发明名称 |
PROCESS FOR REGIOSELECTIVE N(5)-FORMYLATION OF (6S)-5,6,7,8-TETRAHYDROPTEROIC ACID AND DERIVATIVES THEREOF |
摘要 |
The process according to the invention for regioselective N(5)-formylation of (6S)-5,6,7,8-tetrahydropteroic acid and derivatives thereof which are defined in formula (I) is characterized in that an aqueous buffer solution having a pH of from 6.5 to 7.5 is added to a mixture of a compound of the formula (I), an antioxidant and a formyl donor in a reaction vessel; an inert gas is blown through the resulting suspension; then an aqueous solution of a base is added dropwise or in portions with constant stirring until a clear solution which has a pH between 6.5 and 8.3 is formed; then a recombinant monofunctional glutamate formyl transferase, abbreviated to rGFT, i.e. the enzyme, is added in an aqueous buffer solution defined above; then the temperature is increased to a range of 30°C to 45°C and the reaction mixture is allowed to react until at least 95% of the formyl has been transferred from the formyl donor to the compound of the formula (I), - then the resulting reaction mixture is cooled to a temperature of from 0°C to 5°C; then an aqueous solution of a mineral acid is added dropwise until a pH of from 2.7 to 3.1 has been attained, which precipitates out the crude compound of the formula (II); the stirring is continued over at least 1 hour in order to complete the abovementioned precipitation, and the crude compound of the formula (II) is obtained. |
申请公布号 |
WO2007082402(B1) |
申请公布日期 |
2008.01.03 |
申请号 |
WO2007CH00022 |
申请日期 |
2007.01.18 |
申请人 |
CERBIOS-PHARMA S.A.;ARINI, ACHILLE;COPPOLECCHIA, RAFFAELA;TOGNINI, ANTONIO;MANZOTTI, RAFFAELA;MARAZZA, FABRIZIO |
发明人 |
ARINI, ACHILLE;COPPOLECCHIA, RAFFAELA;TOGNINI, ANTONIO;MANZOTTI, RAFFAELA;MARAZZA, FABRIZIO |
分类号 |
C12P17/18;C12N9/10 |
主分类号 |
C12P17/18 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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