EP0228414A4 - Procede de preparation de 4-hydroxycyclopent-2-en-1-one. - Google Patents

Procede de preparation de 4-hydroxycyclopent-2-en-1-one.

Info

Publication number
EP0228414A4
EP0228414A4 EP19860904009 EP86904009A EP0228414A4 EP 0228414 A4 EP0228414 A4 EP 0228414A4 EP 19860904009 EP19860904009 EP 19860904009 EP 86904009 A EP86904009 A EP 86904009A EP 0228414 A4 EP0228414 A4 EP 0228414A4
Authority
EP
European Patent Office
Prior art keywords
microorganism
atcc
nrrl
hydroxycyclopent
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP19860904009
Other languages
German (de)
English (en)
Other versions
EP0228414A1 (fr
Inventor
Charles J Sih
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wisconsin Alumni Research Foundation
Original Assignee
Wisconsin Alumni Research Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wisconsin Alumni Research Foundation filed Critical Wisconsin Alumni Research Foundation
Publication of EP0228414A1 publication Critical patent/EP0228414A1/fr
Publication of EP0228414A4 publication Critical patent/EP0228414A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/24—Preparation of oxygen-containing organic compounds containing a carbonyl group
    • C12P7/26—Ketones

Definitions

  • the present invention relates to processes for preparing 4-hydroxycyclqpent-2-enones.
  • the same (R)-enanticmer (1) has also been prepared by chemical modification of the fungal metabolite terrein [L. A. itscher et al. Tetrahedron Lett., 2553 (1978)].
  • the opposite 4(S_)- hydroxyclopent-2-enone (2) has been prepared in 86% optical purity from (2R,3R)- or (+)-tartaric acid [K. Ogura et al, (1976) ] and in low enanticmeric excess and overall yield from 3,5-diacetoxycyclopent-l-ene [T. Tanaka et al,' Tetrahedron, 32, 1713 (1976) ] .
  • optically pure enanticmsrs of 1 ⁇ and 2_ have been prepared from phenol via a long reaction sequence and chanical resolution M. Gill and R. W. Richards, Tetrahedron Lett., 1539 (1979)].
  • the present invention provides improved processes for producing racemic and optically-active 4-hydroxycyclopent-2- enones from readily available, moderate cost, raw materials such as cis and trans-3,5-dihydroxycyclcpent-l-ene.
  • the meso diol, c ⁇ s-3,5-d:iI ⁇ ydroxycyclopent-l-ene (3_) can be prepared via a 1,4- ⁇ ycloaddition ot cyclqpentadiene with singlet oxygen [C. Kaneko et al. Synthesis, 876 (1974) ; C. S. Foote and S. exler, J. Am. Chart. Soc., j36_, 3879 (1964)].
  • Mixtures of trans and cis-3,5-dihydroxycyclopent-l-ene can be synthesized frc cis-3,5-dibrcmocyclopent-l-ene [L. N. Oven and P. N. Smith, J. Chem. Soc.
  • the meso-diol, 3_ is a solid (m.p.59-60°C) whereas the racanic trans mixture (4R+4S) is a liquid at room ta ⁇ perature, the meso-diol can be crystallized to yield a semi-solid consisting of approximately three parts of [ and one part of the trans- enanticmers 4R+4S) . Conversely, the mother liquor remaining consists of approximately one part of 3_ and three parts of 4R + 4S.
  • the microbial process of the present invention has a distinct advantage over chemical oxidative methods. It avoids the need of protection-deprotection and the use of expensive oxidative reagents [T. Tanaka et al. Tetrahedron, 32, 1713 (1976) ] .
  • Microorganisns which have the desired oxidative activity are well known in the microbiological art and any of such microorganisms can be employed in conducting the process of the present invention [see K. Kieslich, "Microbial Transformations of Non-Steroid Cyclic Compounds” (Georg Thieme Publishers, Stuttgart, 1976)], with any of the genera of microorganisms specifically set forth herein being particularly suitable.
  • the 3,5-dihydroxycyclopent-l-ene can be incorporated in a nutrient medium of standard composition in which such organisms are cultivated and the usual conditions of fermentation which are well kncwn in the art can then be employed to effect the oxidative transformation.
  • the active principle can be removed from the growing culture of the microorganisms, for example, by lysis of the cells to release the enzymes, or by suspension of the resting cells in a fresh aqueous medium.
  • the cells and the enzyme can be immobilized in accordance with well kncwn procedures to further reduce the cost of the process.
  • an alcoholic function will be selectively oxidized as long as the active enzyme elaborated by the microorganism is present.
  • the temperature, time and pressure conditions under which the contact of the cyclopentenediol with the oxidative enzyme is carried out are interdependent as will be understood and readily apparent to those skilled in the art. For example, with gentle heating and at atmospheric pressure, the time required will be less than if the reaction progresses at room temperature under conditions otherwise the same. Neither temperature, nor pressure, nor time should be permitted to exceed limits that will result in the substrate being degraded. Where a growing culture of the organism is being used, the process conditions should also be sufficiently gentle so the organism is not killed before it elaborates sufficient proteolytic enzymes to permit destruction of the oxidative enzyme. Generally, at atmospheric pressure, the reaction can be carried out at a temperature in the range frc about 10° to about 35°C, for from about 12 hours to about 10 days.
  • microorganisms of the orders Moniliales, End ⁇ nycetales, Eubacteriales and Eurotiales have been found to be particularly suitable in the method of this invention. It has been observed, however, that there are variations in the efficiency with which different orders, genera, and species of microorganisms accomplish the oxidative process of this ivnention. Also, relative efficiency of a given organism to accomplish such oxidation and the relative proportion of 4- hydroxycycl ⁇ pent-2-en-l-one a d 4-hydroxycycl ⁇ pentan-l-one formed can be severaly affected by the ccmposition of the fermentation medium.
  • microorganisms were maintained on agar slants of the following composition: a) Bacteria Gms
  • Rhodococcus sp ATCC 19070 was grown for 48 hrs in medium B and the cells were collected by centrifugation.
  • Phenazine methosulface (5 x 10 M) was added to 2 g of wet cell paste, suspended in 20 ml of 50 mM potassium phosphate buffer, pH 7.5. After incubation on a rotary shaker for 5 minutes at 25°C, 20 mg of cis-3,5-dihydroxycyclopent-l-ene
  • the column was eluted with CHCl_-diethyl ether-hexane (1:4:16) at a flow rate of 1.5 ml per min and the absorbance at 254 nm was monitored.
  • the retention times were: JL(R) : 22 min and _2(S) : 19 min.
  • the enanticmeric excess (ee) was calculated by quantitatively measuring the peak areas of diasterecmers.
  • the sample of JL derived from Rhodococcus sp. ATCC 19070, was established to have an ee of 0.70.
  • EXAMPLES 52-57 Using the same procedures as example 51 with the growth media and conditions specified below, the following microorganisms transformed cis-3,5-dihydroxycyclopent-l-ene (3_) into either 4R-hydroxycyclopent-2-en-l-one (1) or 4&-hydroxycyclopent-2-en-l-one (2_) of varying optical purity.
  • EXAMPLE 59 The procedure of example 51 was repeated using Mycobacterium sp. NRRL 15051 in absence of phenazine methosulfate to give 4R.-hy ⁇ roxycyclopentan-l-one (5R) in high yield.
  • EXAMPLE 60 The procedure of example 51 was repeated using Mycobacterium sp. NRRL 15051 except that (+)trans-cycl ⁇ pent- 2-ene-l,4-diol 4R + ⁇ S) was used as the substrate to give 4R-hydroxycyclcpent-2-en-l-one (1) in good yield.
  • EXAMPLE 61 The procedure of example 51 was repeated except that 1,4-naphthoquinone was substituted for phenazine methosulfate to give 4R-hydroxycyclopent-2-en-l-one (1) in high yield.
  • EXAMPLE 62 The procedure of example 51 was repeated except that menadione was substituted for phenazine methosulfate. 4R- hydroxycyclopent-2-en-l-one (1) was recovered in high yield.
  • EXAMPLE 63 The procedure of example 51 was repeated except that 1,2- naphthoquinone was substituted for phenazine methosulfate. 4R-hydroxycyclopent-2-en-l-one (JL) was recovered in high yield.
  • EXAMPLE 64 The procedure of example 51 was repeated except that potassium ferricyanide was substituted for phenazine methosulfate. 4R-hydroxycyclopent-2-en-l-one (1) was recovered in high yield. EXAMPLE 65
  • microorganisms of the Orders and Species specified can be genetically engineered or mutated by well known methods to increase their capability for preferentially expressing enzymes which will enhance the production of the desired 4-hydroxycyclopent-2-enones or to mir mize or eliminate the expression of enzymes which would interfere with the desired reactivity.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
EP19860904009 1985-06-21 1986-06-13 Procede de preparation de 4-hydroxycyclopent-2-en-1-one. Withdrawn EP0228414A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US74754085A 1985-06-21 1985-06-21
US747540 1985-06-21

Publications (2)

Publication Number Publication Date
EP0228414A1 EP0228414A1 (fr) 1987-07-15
EP0228414A4 true EP0228414A4 (fr) 1989-08-09

Family

ID=25005526

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19860904009 Withdrawn EP0228414A4 (fr) 1985-06-21 1986-06-13 Procede de preparation de 4-hydroxycyclopent-2-en-1-one.

Country Status (2)

Country Link
EP (1) EP0228414A4 (fr)
WO (1) WO1986007611A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3415716A (en) * 1966-05-17 1968-12-10 Hoffmann La Roche Preparation of hydroxycyclopentenones
FR2324608A1 (fr) * 1974-12-27 1977-04-15 Teijin Ltd Derives de l'hydroxy-4 cyclopentene-2-one-1 utilisables pour la fabrication de medicaments, et preparation de ces substances

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4375515A (en) * 1979-03-27 1983-03-01 Exxon Research And Engineering Co. Method for producing microbial cells and use thereof to produce oxidation products
JPS57141295A (en) * 1981-02-27 1982-09-01 Sagami Chem Res Center Preparation of ketone

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3415716A (en) * 1966-05-17 1968-12-10 Hoffmann La Roche Preparation of hydroxycyclopentenones
FR2324608A1 (fr) * 1974-12-27 1977-04-15 Teijin Ltd Derives de l'hydroxy-4 cyclopentene-2-one-1 utilisables pour la fabrication de medicaments, et preparation de ces substances

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO8607611A1 *

Also Published As

Publication number Publication date
WO1986007611A1 (fr) 1986-12-31
EP0228414A1 (fr) 1987-07-15

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