Chemistry: molecular biology and microbiology – Process of utilizing an enzyme or micro-organism to destroy... – Resolution of optical isomers or purification of organic...
Patent
1991-04-01
1994-01-04
Knode, Marian C.
Chemistry: molecular biology and microbiology
Process of utilizing an enzyme or micro-organism to destroy...
Resolution of optical isomers or purification of organic...
435126, 435171, 435136, 4352541, 4352561, 4352565, 4352563, 4352566, C12P 4100, C12P 740
Patent
active
052759490
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INDUSTRIAL APPLICATION
The present invention relates to a process for the preparation of D-pantolactone, a useful intermediate in the preparation of D-pantothenic acid and pantethine, both useful as vitamins of medical or physiological importance.
PRIOR ART
D-pantolactone has heretofore been prepared through optical resolution of chemically synthesized D,L-pantolactone.
Such process, however, requires the use of costly resolving agents such as quinine or brucine, and has the disadvantage that the recovery of D-pantolactone is not easily carried out.
Processes of enzymatically resolving D,L-pantolactone are also known, and the following processes have heretofore been reported:
In Japanese Examined Patent Application Publication No. 19745/72 (TOKKO-SHO 47-19745) is described a process of obtaining only D-pantolactone by using microorganisms to completely decompose L-pantolactone in D,L-pantolactone. This process, however, has the drawback that half the amount of D,L-lactone is lost.
In Japanese Unexamined Patent Application Publication No. 293386/86 (TOKKAI-SHO 61-293386) is described a process wherein only L-pantolactone in D,L-pantolactone is oxidized by the use of microorganisms into ketopantolactone, which is then converted by asymmetric reduction into D-pantolactone. This process, however, is of little practical significance due to the fact that both the substrate concentration and the reaction rate are low.
In Japanese Unexamined Patent Application Publication Nos. 152895/82 (TOKKAI-SHO 57-152895) and 294092/87 (TOKKAI-SHO 62-294092) are described processes wherein the L-form in D,L-pantolactone is selectively subjected to asymmetric hydrolysis by microorganisms to afford D-pantolactone. These processes are not practical because both the substrate concentration and the reaction rate are low, and D-pantolactone of high optical purity can be obtained only when the L-form has been completely hydrolyzed.
DISCLOSURE OF THE INVENTION
As a result of extensive researches on the asymmetric hydrolysis of D,L-pantolactone, the present inventors have now found that D-pantolactone can be obtained efficiently from D,L-pantolactone through selective asymmetric hydrolysis by certain microorganisms of only the D-form in D,L-pantolactone to form D-pantoic acid, followed by separation and conversion thereof into D-pantolactone. The present invention has been predicated on such findings.
Accordingly, the present invention provides a process for the preparation of D-pantolactone, comprising selectively subjecting the D-form in D,L-pantolactone to asymmetric hydrolysis employing a microorganism possessing the ability to effect said selective asymmetric hydrolysis selected from the group consisting of the genera Fusarium, Cylindrocarpon, Gibberella, Aspergillus, Penicillium, Rhizopus, Volutella, Gliocladium, Eurotium, Nectria, Schizophyllum, Myrothecium, Neurospora, Acremonium, Tuberculina, Absidia, Sporothrix, Verticillium and Arthroderma to form D-pantoic acid, which is then separated and converted into D-pantolactone, followed by recovery thereof.
As compared to the above-mentioned known processes of selective asymmetric hydrolysis of the L-form in D,L-pantolactone, the present invention has many advantages. For example higher substrate concentrations may be used, shorter reaction times may be employed, and D-pantolactone of extremely high optical purity can be obtained.
The following describes the present invention in more detail.
The inventors inoculated 5 ml portions of different liquid media with seed cultures from slants. The seeded media were subjected to aerobic shake culture at 28.degree. C. for 2-7 days and then to centrifugation or filtration to collect the cells. To the cells were added 2 ml of 2% D,L-pantolactone solution in 0.2M Tris-HCl buffer, and the mixture was shaken overnight at 28.degree. C. The resultant reaction liquid was subjected to HPLC and GLC to measure the decrease of pantolactone and the amount of pantoic acid formed, and to determine the optical purity of pantolactone, respec
REFERENCES:
patent: 3600279 (1971-08-01), Takahashi et al.
patent: 3850750 (1974-11-01), Lanziolotta
Sakamoto Keiji
Shimizu Sakayu
Yamada Hideaki
Fuji Yakuhin Kogyo Kabushiki Kaisha
Knode Marian C.
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