Process for the production of piperidine derivatives with microorganisms
View Patent ↗The present invention relates to the production of a product compound having a structure according to Formulae IA and/or IB: wherein n is 0 or 1; R 1 is hydrogen or hydroxy; R 2 is hydrogen; or, when n is 0, R 1 and R 2 taken together form a second bond between the carbon atoms bearing R 1 and R 2 , provided that when n is 1, R 1 and R 2 are each hydrogen; R 3 is —COOH or —COOR 4 ; R 4 is an alkyl or aryl moiety; A, B, and D are the substituents of their rings, each of which may be different or the same, and are selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, and alkoxy. This process involves incubating a starting compound having a structure according to Formulae IIA and/or IIB: wherein R 3 is —CH 3 and R 1 , R 2 , A, B, and D are defined above in the presence of a microorganism under conditions effective to produce the product compound. The microorganism can be from the genus Streptomyces, Stemphylium, Gliocladium, Bacillus, Botrytis, Cyathus, Rhizopus, Pycniodosphora, Pseudomonas, Helicostylum, Aspergillus, Mucor, Gelasinospora, Rhodotorula, Candida, Mycobacterium , or Penicilluc . Alternatively, the microorganism can be Cunninghamella baineri.
1. A process for production of a product compound having a structure according to Formulae IA and/or IB:
wherein
n is 0 or 1;
R 1 is hydrogen or hydroxy;
R 2 is hydrogen;
or, when n is 0, R 1 and R 2 taken together form a second bond between the carbon atoms bearing R 1 and R 2 , provided that when n is 1, R 1 and R 2 are each hydrogen;
R 3 is —COOH or —COOR 4 ;
R 4 is an alkyl moiety;
A, B, and D are the substituents of their rings, each of which may be different or the same, and are selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, and alkoxy,
said process comprising:
incubating a starting compound having a structure according to Formulae IIA and/or IIB:
wherein R 3 * is —CH 3 and R 1 , R 2 , A, B, and D are defined above, in the presence of a microorganism under conditions effective to produce the product compound, wherein the microorganism is Bacillus cereus, Bacillus subtilis , or Bacillus fusiformis.
2. The process according to claim 1 , wherein the product compound has a structure according to Formula IVA and/or IVB:
wherein R 1 , R 2 , R 3 , A, B, and D are defined above.
3. The process according to claim 1 , wherein prior to said incubating, the microorganism is subjected to cryopreservation or multi-stage liquid culture induction.