Enantioselective trans dihydroxylation of nonactivated C-C double bonds of aliphatic heterocycles with Sphingomonas sp. HXN-200.
The bacterial strain Sphingomonas sp. HXN-200 was used to catalyze the trans dihydroxylation ofN-substituted 1,2,5,6-tetrahydropyridines 1 and 3-pyrrolines 4 giving the corresponding 3,4-dihydroxypiperidines 3 and 3,4-dihydroxypyrrolidines 6, respectively, with high enantioselectivity and high activity. The trans dihydroxylation was sequentially catalyzed by a monooxygenase and an epoxide hydrolase in the strain with epoxide as intermediate. While both epoxidation and hydrolysis steps contributed to the overall enantioselectivity in trans dihydroxylation of 1, the enantioselectivity in trans dihydroxylation of the symmetric substrate 4 was generated only in the hydrolysis of meso-epoxide 5. The absolute configuration for the bioproducts (+)-3 and (+)-6 was established as (3R,4R) by chemical correlations. Preparative trans dihydroxylation of 1a and 4b with frozen/thawed cells of Sphingomonas sp. HXN-200 afforded the corresponding (+)-(3R,4R)-3,4-dihydroxypiperidine 3a and (+)-(3R,4R)-3,4-dihydroxy pyrrolidine 6b in 96% ee both and in 60% and 80% yield, respectively. These results represent first examples of enantioselective trans dihydroxylation with nonterpene substrates and with bacterial catalyst, thus significantly extending this methodology in practical synthesis of valuable and useful trans diols. Enantioselective hydrolysis of racemic epoxide 2a with Sphingomonas sp. HXN-200 gave 34% of (-)-2a in >99% ee, which is a versatile chiral building block. Further hydrolysis of (-)-2a with the same strain afforded (-)-(3S,4S)-3a in 96% ee and 92% yield. Thus, both enantiomers of 3a can be prepared by biotransformation with Sphingomonas sp. HXN-200.
Institute of Biotechnology, ETH-Hönggerberg, CH-8093 Zurich, Switzerland.
Dongliang
D
Chang
Maarten F
MF
Heringa
Bernard
B
Witholt
Zhi
Z
Li
D002384:Catalysis; D002460:Cell Line; D004851:Epoxide Hydrolases / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry; D006868:Hydrolysis; D006900:Hydroxylation; D008956:Models, Chemical; D011726:Pyridinium Compounds / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000737:chemistry; D020578:Sphingomonas / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013997:Time Factors
D004852:Epoxy Compounds; D011726:Pyridinium Compounds; D011759:Pyrrolidines; D004851:Epoxide Hydrolases