Reacción #1527

Ecuación de reacción

sodium hydroxide

sulfuric acid

(3S)-1-chloro-3-methoxycarbonylamino-4-phenyl-2-butanone

→

(2S,3S)-1-chloro-3-methoxycarbonylamino-4-phenyl-2-butanol

Rendimiento 61.0%

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroA culture was obtained by the same method as in Example 1 using Candida gropengiesseri IFO 0659 as the microorganism
2. 2
   OtroA 75-ml portion of this culture was separated into a supernatant and cells by centrifugation
3. 3
   workup.ADDITIONTo the whole amount of the cells was added a portion of the supernatant
4. 4
   workup.ADDITIONThis cell suspension (25 ml), 1 g of glucose and 250 mg of (3S)-1-chloro-3-methoxycarbonylamino-4-phenyl-2-butanone were mixed together in a 500-ml Sakaguchi flask
5. 5
   Otrothe reaction
6. 6
   workup.STIRRINGby shaking for further 6 days
7. 7
   Concentraciónthe glucose concentration within the range of 0 to 4%
8. 8
   workup.ADDITIONby adding glucose portionwise
9. 9
   workup.ADDITIONWater, 100 ml, was added to the reaction mixture
10. 10
    Extracciónthe whole mixture was extracted with 100 ml portion of ethyl acetate for 3 times
11. 11
    Lavadowashed with 100 ml of water and further with 100 ml of a saturated aqueous sodium chloride solution
12. 12
    Secadodried over anhydrous sodium sulfate
13. 13
    ConcentraciónThis solution was concentrated to dryness

Procedimiento

A culture was obtained by the same method as in Example 1 using Candida gropengiesseri IFO 0659 as the microorganism and adjusted to pH 6 with an aqueous sodium hydroxide solution and an aqueous sulfuric acid solution. A 75-ml portion of this culture was separated into a supernatant and cells by centrifugation. To the whole amount of the cells was added a portion of the supernatant to make the total volume 25 ml. This cell suspension (25 ml), 1 g of glucose and 250 mg of (3S)-1-chloro-3-methoxycarbonylamino-4-phenyl-2-butanone were mixed together in a 500-ml Sakaguchi flask and the mixture was shaken for 1 day to allow the reaction to proceed. A further 250-mg portion of (3S)-1-chloro-3-methoxycarbonylamino-4-phenyl-2-butanone was added. The reaction was allowed to proceed by shaking for further 6 days while controlling the glucose concentration within the range of 0 to 4% by adding glucose portionwise. Water, 100 ml, was added to the reaction mixture and the whole mixture was extracted with 100 ml portion of ethyl acetate for 3 times. The organic extract layers were combined, washed with 100 ml of water and further with 100 ml of a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. This solution was concentrated to dryness to give (2S,3S)-1-chloro-3-methoxycarbonylamino-4-phenyl-2-butanol as a white solid (401 mg; yield 61%; purity 76.8 wt %; selectivity 2S,3S/2R,3S=98/2; optical purity 98.3% ee).

Fuente