Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1993-01-04
1994-07-05
Bond, Robert T.
Organic compounds -- part of the class 532-570 series
Organic compounds
Unsubstituted hydrocarbyl chain between the ring and the -c-...
540455, C07D49816
Patent
active
053268628
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The (2-dialkylaminoalkyl)-26-sulphinylpristinamycin II.sub.B of general formula: ##STR1## in which Alk represents a straight-chain or branched alkylene radical and R represents straight-chain or branched alkyl radicals, these radicals containing 1 to 10 carbon atoms, are products known for their antibacterial activity and their synergistic action on the antibacterial activity of pristinamycin I.sub.A or alternatively as synthetic intermediates for preparing the corresponding sulphones, as has been described in European Patent 191,662.
DESCRIPTION OF THE INVENTION
The derivatives of pristinamycin II.sub.B of general formula (I) can be obtained by oxidation of the corresponding sulphide, especially according to the teaching of European Patent 191,662 which describes the oxidation of a sulphide of formula: ##STR2## in which Alk and R are as defined above, by an organic or inorganic peracid.
American U.S. Pat. No. 4,775,753 likewise describes the production of (2-dialkylaminoalkyl)-26-sulphinylpristinamycin II.sub.B of general formula (I) starting from (2-dialkylaminoalkyl)-26-thiopristinamycin II.sub.B of general formula (II) by oxidation by Oxone.
It has now been found that (2-dialkylaminoalkyl)-26-sulphinylpristinamycin II.sub.B of general formula (I) can be obtained by oxidation of the corresponding sulphide of general formula (II) by hydrogen peroxide, in the presence of sodium tungstate, working in alcoholic medium at a temperature between -25.degree. and 25.degree. C.
It is necessary to introduce the oxidizing agent in excess relative to the quantity of product to be oxidized. The hydrogen peroxide employed can be introduced at a rate of 2 to 5 equivalents. Most generally, it is employed at a rate of approximately 2 equivalents per mole of sulphide of pristinamycin II.sub.B.
It is understood that the reaction temperature will be fixed as a function of the number of equivalents of oxidizing agent employed. When the reaction is carried out in the presence of 2 equivalents of hydrogen peroxide, the temperature may vary from -25.degree. to +25.degree. C. When the reaction is carried out in the presence of 5 equivalents of oxidizing agent, the reaction is carried out at between -25.degree. and -10.degree. C.
The preferred alcoholic solvent is ethanol, but it is likewise possible to work in methanol or isopropanol.
This process has the advantage of giving access to a product of a higher degree of purity while avoiding purification by chromatography, and thereby allows a very distinct improvement in the yield. Moreover, when the product of formula (I) thus obtained is to be used subsequently for the preparation of (2-dialkylaminoalkyl ) -26 -sulphonylpristinamycin II.sub.B of general formula: ##STR3## in which Alk and R are as defined above, the derivative of pristinamycin II.sub.B of general formula (I) is of sufficient quality to enable the crude product to be used directly in the subsequent oxidation step, for example according to the process of European Patent Application 252,720, without it being necessary to first carry out chromatography, recrystallization or filtration over silica as was the case for the previously known processes. An improved total yield and likewise a simplification of the implementation of the process result thereby.
EXAMPLES
The following examples, given without implying a limitation, illustrate the present invention.
EXAMPLE 1
2.635 g (4 mM) of (2-diethylaminoethyl)-26-thiopristinamycin II.sub.B isomer A, suspended in 16 cm.sup.3 of absolute ethanol, are placed in an ice bath. A solution of 13.2 mg (0.04 mM; 1 mol %) of sodium tungstate dihydrate in 0,906 g (8 mM, 2 equivalents) of hydrogen peroxide (30%) is then added in the course of 2 minutes at a temperature of 1.degree. to 2.degree. C. The suspension of sulphide becomes clear. Stirring is continued for 1 hour and 5 minutes in total.
5 cm.sup.3 of water are added to the reaction mixture at 0.degree. C. After stirring for 5 minutes, the solution is extracted with 40 cm.sup.3 of methylene chlorid
REFERENCES:
March "Advanced Organic Chemistry" 3rd Ed. (1985) (Wiley) pp. 1089-1090.
Noller "Chemistry of Organic Compounds" 2nd Ed. (1957) (Saunders) pp. 278-279.
European Search Report.
Bond Robert T.
Rhone-Poulenc Rorer S.A.
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