EP0139681A1 - PROCEDE PHOTOCHIMIQUE POUR LA FABRICATION DE PREVITAMINE D 2? et D 3? A PARTIR D'ERGOSTEROL, RESPECTIVEMENT DE 7-DESHYDROCHOLESTEROL - Google Patents

PROCEDE PHOTOCHIMIQUE POUR LA FABRICATION DE PREVITAMINE D 2? et D 3? A PARTIR D'ERGOSTEROL, RESPECTIVEMENT DE 7-DESHYDROCHOLESTEROL

Info

Publication number
EP0139681A1
EP0139681A1 EP19840901189 EP84901189A EP0139681A1 EP 0139681 A1 EP0139681 A1 EP 0139681A1 EP 19840901189 EP19840901189 EP 19840901189 EP 84901189 A EP84901189 A EP 84901189A EP 0139681 A1 EP0139681 A1 EP 0139681A1
Authority
EP
European Patent Office
Prior art keywords
laser
previtamin
lasers
dehydrocholesterol
group
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.)
Pending
Application number
EP19840901189
Other languages
German (de)
English (en)
Inventor
Karl-Ludwig Kompa
Werner Fuss
Michael Braun
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.)
Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Original Assignee
Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
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 Max Planck Gesellschaft zur Foerderung der Wissenschaften eV filed Critical Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Publication of EP0139681A1 publication Critical patent/EP0139681A1/fr
Pending legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
    • B01J19/12—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electromagnetic waves
    • B01J19/121—Coherent waves, e.g. laser beams

Definitions

  • the invention relates to a photochemical process for producing previtamin D 2 and D 3 from 7-dehydrocholesterol and ergosterol, respectively.
  • previtamins D 2 and D 3 from 7-dehydrocholesterol or ergosterol by irradiation. These previtamins can be converted into the more thermally stable vitamins D 2 and D 3 by thermal rearrangement.
  • previtamin D 3 absorbs an ever increasing proportion of the light with increasing conversion.
  • the quantum yield of the subsequent photochemical reaction of previtamin D 3 to tachysterin, the trans-isomeric triene is greater than the quantum yield of its formation. You are therefore forced. stop the exposure of 7-dehydrocholesterol at a conversion of 30 to 50% and isolate the previtamin D 3 .
  • Another problem with this photo-chemical synthesis is that the emission of the mercury lamp is very poorly matched to the spectrum of 7-dehydrocholesterol.
  • the main emission of the mercury lamp is 254 nm, a wavelength that favors the development of the undesired tachysterin (see Fig. 1 of the drawing).
  • In the most favorable wavelength range there are only three very weak lines at 280, 289 and 297 nm, which add up to a total of 8.5 hol quanta / hour for a kW lamp (total emission for all wavelengths: 174 mole quanta / hour).
  • Secondary products can be suppressed by irradiation at wavelengths at which the ratio of the absorption cross-sections of the starting product to that of the primary product is greatest; ie at wavelengths in the range from 270 to 300 nm, and in particular wavelengths in the range of the adsorption maxima of the starting product. In these areas, however, the unwanted by-products absorb in comparison to Primary product very strong.
  • a measure of the composition of the mixture to be achieved is the photostationary state, ie the state which would be reached if the irradiation was sufficiently long (see, for example, BE Abillon and R. Mermet-Bouevier, J. Pharm. Sei. 62 (1973) 1691; T. Kobayashi and M. Yasumura, J. Nutr. Sei. Vitaminol 19 (1973) 123; and K. Pfoertner and JP Weber, Helv. Chim. Acta 55 (1972) 921).
  • the object of the present invention is therefore to overcome the disadvantages mentioned and to provide a photochemical process for the preparation of previtamin D 2 and D 3 from 7-dehydrocholesterol which can be carried out easily and with good yields even on an industrial scale. This object is achieved with the present invention.
  • the invention relates to a photochemical process for the production of previtamin D 2 and D 3 from ergosterol and 7-dehydrocholesterol, respectively, which is characterized in that a laser is used as the radiation source, which
  • (a) is an energy-rich laser that has wavelengths outside the range required for previtamin D synthesis, but delivers a pulsed light with high photon yields in the desired wavelength range by one or more Raman shifts of the emitted wavelengths,
  • (b) is a laser from the group of excimer lasers
  • (d) is a laser from the group of metal vapor lasers with frequency doubling.
  • previtamin D 2 and D 3 are understood to mean all those previtamin D substances which have the same spectral properties as previtamin D 2 and D 3 themselves.
  • the radiation sources according to the invention can be used either in a one-stage photochemical process which leads directly to previtamin D from 7-dehydrocholesterol, or else in a two-stage process.
  • tachysterin is first formed; As the only component of the reaction mixture obtained, this has a significant absorption even at wavelengths> 300 nm and can be performed with a second irradiation with a longer-wave light source (see WG Dauben and RB Phillips, JACS 104 (1982) 335) or by triplet sensitization (see e.g. BSC Eyley and DH Williams, JCS Chem. Comm. (1975) 858; M. Denny and RSH Liu, Nouv. J.
  • the lasers according to the invention are surprisingly well suited in the wavelength range between 270 and 295 nm as a technically useful radiation source for the first stage.
  • the higher proportion of the desired product significantly shortens the second stage, which is more complex because of the low absorption coefficients.
  • High-energy lasers are used as the laser (a) according to the invention, the wavelength of which lies outside the optimum range required for the previtamin D synthesis, but which provide pulsed light with high photon yields in the desired wavelength range due to one or more Raman shifting of the emitted wavelengths.
  • these lasers it is possible to use both those that are shifted from wavelengths that are too short by Raman shifting into the longer-wave range (so-called Stokes-Raman lasers), and those that are too long-wavelength that are shifted into the shorter-wave range (so-called anti-Stokes Raman laser).
  • Typical examples with which good results can be obtained are StokesRaman-shifted KrF and ArF lasers and anti-StokesRaman-shifted XeCl lasers. Because of the high efficiencies that have now been achieved (e.g. 70% energy conversion into the second Stokes wavelength according to JN Holliday, Opt. Lett. 8, 12 (1983)), the lasers working according to this principle are quite suitable for a representation on a technical scale .
  • Halogen lasers such as, for example, are suitable as excimer lasers.
  • An exciplex laser used according to the invention is in particular a xenon bromide laser (282 nm).
  • a xenon bromide laser (282 nm).
  • Such a laser is two different reactants, e.g. B. noble gas and halogen, which give an emitting molecule under the excitation conditions.
  • a copper vapor laser at 578 nm with frequency doubling is preferred as the metal vapor laser with frequency doubling to be used according to the invention.
  • Some of the lasers used according to the invention are lasers known per se (see, for example, IEEE Journal of Quantum Electronics, Vol. QE-15, No. 5, May 1979, 337; (Applied Physics Letters, Vol. 28, No. 9, 530 and Vol. 32, No. 8, 479; Appl. Physics 23, 1980, 283-287)) or, e.g. B. in Raman shifted lasers using CO 2 as Raman medium to new laser systems.
  • these lasers When applied to photochemical previtamin D syntheses, these lasers have proven to be surprisingly good and powerful radiation sources.
  • the method of the invention is equally suitable for the preparation of the hydroxylated or a ⁇ ylated previtamin D derivatives, e.g. B. of 1-hydroxy- or 25-hydroxy or acyloxi drapevitamin D, and of other previtamin D derivatives which have the same spectral properties.
  • 7-dehydrocholesterol was dissolved in 0.5% ethanolic solution using a multiple shifted anti-Stokes Raman dye laser with H 2 as Raman medium at 294.5 and 282.5 nm and for comparison with the KrF laser at 248.3 nm irradiated in a quartz cuvette with exclusion of air.
  • the composition was determined at regular intervals by liquid chromatography. At 294.5 nm (see FIG. 2 of the drawing), that is to say close to the mathematically most favorable wavelength of approximately 296 nm, with approximately 50% conversion, more than 80% of the products consist of the desired previtamin D 3 .
  • the starting material can be easily separated by known methods.
  • the continuation of the irradiation until the photostationary state led to a good agreement with the calculated product composition (see FIG. 3 of the drawing). Due to the quantum yield of 27% obtained, the process is also suitable for use on an industrial scale.

Landscapes

  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Optics & Photonics (AREA)
  • Electromagnetism (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Toxicology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Le procédé se caractérise par le fait que l'on utilise comme source d'irradiation un laser (a) qui est un laser de haute énergie, possédant des longueurs d'onde situées en-dehors de la zone requise pour la synthèse de la prévitamine D, mais émettant par déplacement Raman simple ou multiple des longueurs d'onde émises une lumière pulsée à rendement élevé en photons dans la zone de longueur d'onde désirée, (b) qui appartient au groupe des lasers excimer, (c) qui appartient au groupe des lasers exciplex, ou (d) qui appartient au groupe des lasers à vapeur métallique avec doublement de fréquence.
EP19840901189 1983-03-10 1984-03-09 PROCEDE PHOTOCHIMIQUE POUR LA FABRICATION DE PREVITAMINE D 2? et D 3? A PARTIR D'ERGOSTEROL, RESPECTIVEMENT DE 7-DESHYDROCHOLESTEROL Pending EP0139681A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3308592 1983-03-10
DE19833308592 DE3308592C2 (de) 1983-03-10 1983-03-10 Photochemisches Verfahren zur Herstellung von Prävitamin D↓2↓ und D↓3↓ aus Ergosterin bzw.7-Dehydrocholesterin

Publications (1)

Publication Number Publication Date
EP0139681A1 true EP0139681A1 (fr) 1985-05-08

Family

ID=6193117

Family Applications (2)

Application Number Title Priority Date Filing Date
EP19840901189 Pending EP0139681A1 (fr) 1983-03-10 1984-03-09 PROCEDE PHOTOCHIMIQUE POUR LA FABRICATION DE PREVITAMINE D 2? et D 3? A PARTIR D'ERGOSTEROL, RESPECTIVEMENT DE 7-DESHYDROCHOLESTEROL
EP84102593A Withdrawn EP0118903A1 (fr) 1983-03-10 1984-03-09 Procédé photochimique de préparation de prévitamine D2 et D3 au départ d'ergostérol ou de 7-déhydro cholestérol

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP84102593A Withdrawn EP0118903A1 (fr) 1983-03-10 1984-03-09 Procédé photochimique de préparation de prévitamine D2 et D3 au départ d'ergostérol ou de 7-déhydro cholestérol

Country Status (3)

Country Link
EP (2) EP0139681A1 (fr)
DE (1) DE3308592C2 (fr)
WO (1) WO1984003509A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IN188477B (fr) 1998-06-23 2002-09-28 Hoffmann La Roche
GB9824246D0 (en) 1998-11-06 1998-12-30 Kelsill Limited Electronic circuit
CN101668739A (zh) * 2007-04-24 2010-03-10 帝斯曼知识产权资产管理有限公司 用于制造前维生素d的光化学方法
US10336694B2 (en) 2014-12-18 2019-07-02 Nucelis Llc Methods for improved production of vitamins D2 and D3
CN110790807B (zh) * 2019-11-04 2021-08-06 广西师范大学 利用LED光源制备9β,10α-去氢黄体酮二乙二缩酮的方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4388242A (en) * 1982-03-15 1983-06-14 Canadian Patents & Development Limited Method of production of vitamin-D

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8403509A1 *

Also Published As

Publication number Publication date
EP0118903A1 (fr) 1984-09-19
WO1984003509A1 (fr) 1984-09-13
DE3308592A1 (de) 1984-09-13
DE3308592C2 (de) 1986-08-07

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PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

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Free format text: VERFAHREN ABGESCHLOSSEN INFOLGE VERBINDUNG MIT 84102593.5/0118903 (EUROPAEISCHE ANMELDENUMMER/VEROEFFENTLICHUNGSNUMMER) VOM 23.07.85.

RIN1 Information on inventor provided before grant (corrected)

Inventor name: FUSS, WERNER

Inventor name: BRAUN, MICHAEL

Inventor name: KOMPA, KARL-LUDWIG