Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1993-01-04
1993-12-21
Bond, Robert T.
Organic compounds -- part of the class 532-570 series
Organic compounds
Unsubstituted hydrocarbyl chain between the ring and the -c-...
C07D49814, A61K 3142
Patent
active
052722660
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a new pristinamycin II.sub.B derivative of formula: ##STR1## as well as to their preparation.
BACKGROUND OF THE INVENTION
Pristinamycin II.sub.B derivatives have been described previously in American Patents U.S. Pat. No. 4,590,004 and U.S. Pat. No. 4,668,669. These products have the property of synergizing the antimicrobial activity of pristinamycin I.sub.A.
Vinyl sulphones are useful products as synthesis intermediates, especially in carrying out Michael reactions. Their preparation is generally performed in several steps, among which an oxidation step and often the isolation of an intermediate sulphone take place, since the preparation is performed in most cases by proceeding via a thiol.
DESCRIPTION OF THE INVENTION
It is found that the vinyl sulphone of formula (I) could be obtained in high yield in one oxidation step, after introducing the sulphur bearing an appropriate functional group at the .beta.-position.
According to the invention, the vinyl sulphone derived from pristinamycin II.sub.B may be prepared by oxidation of a 26-[2-(dialkylamino)ethylthio]pristinamycin II.sub.B of general formula: ##STR2## in which Alk is an alkyl radical containing 1 to 4 carbon atoms in a straight or branched chain, with 4 to 6 equivalents of hydrogen peroxide in the presence of a catalyst such as ammonium molybdate or sodium tungstate.
This new technique has the advantage of being very gentle and very specific. It may hence be applied to delicate molecules containing a large number of functions capable of being adversely affected by the reaction, as is the case with the component II of pristinamycin.
The reaction is performed in an alcohol, such as, for example, ethanol, methanol or isopropanol, at a temperature of between -25.degree. and +25.degree. C. The quantity of catalyst, expressed in moles % is introduced in the proportion of 1 to 7 % of the starting thioether.
It is essential to work in the presence of a large excess of hydrogen peroxide: in the proportion of 4 to 6 equivalents per mole of sulphide employed in the reaction. Preferably, the reaction is performed in the presence of 5 equivalents of oxidizing agent.
In the case of a reaction catalyzed by sodium tungstate, it is understood that the reaction may be carried out at low temperature, but it is necessary for the last part of the reaction to be carried out at a temperature not below 0.degree. C.
Another advantage of the new process according to the invention is that of enabling vinyl sulphones derived from pristinamycin II.sub.B to be obtained in high yields and without subsequent purification.
The 26-[2-(dialkylamino)ethylthio]pristinamycin II.sub.B of general formula (II) may be obtained as described in U.S. Pat. No. 4,590,004.
The vinyl sulphone according to the invention is useful as an intermediate for the preparation of pristinamycin II.sub.B derivatives of general formula: ##STR3## in which R is a linear or branched alkyl radical containing 1 to 10 carbon atoms, by the action of the amine of general formula:
The reaction is generally performed in a chlorinated solvent such as, for example, methylene chloride, at a temperature of between 0.degree. and 25.degree. C.
The pristinamycin derivatives of general formula (III) are especially advantageous products which are described in U.S. Pat. No. 4,668,669 for their antibacterial activity and their synergistic action on the antibacterial activity of natural pristinamycin I.sub.A, virginiamycin S and soluble derivatives of these products.
EXAMPLE
The examples which follow, given without implied limitation, illustrate the present invention.
EXAMPLE 1
65.9 g (0.1 mol) of 26-[2-(diethylamino)thio]pristinamycin II.sub.B are placed in 400 cm.sup.3 of ethanol and cooled to -20.degree. C. The oxidizing agent (ammonium molybdate: 8.65 g, 7 % +hydrogen peroxide (30 %): 51.5 cm.sup.3, 5 eq.) is added in the course of 20 minutes at between -20.degree. and -15.degree. C. and stirring is continued for 40 minutes at -20.degree. C. In the course o
Bond Robert T.
Rhone-Poulenc Rorer S.A.
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