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 Process for producing parasiticidal milbemycin derivatives by culturing streptomyces

Details
Inventors: Banks, Rhona M.; Baker, Geoffrey H.; Dorgan, Roderick J.; Poulton, Mark E.;
Assignee: Pfizer Inc. (New York, NY)
Primary Examiner: Marx; Irene
Assistant Examiner:
Attorney, Agent or Firm: Richardson; Peter C., Ginsburg; Paul H., Koller; Alan L.

Compounds of formula (I): ##STR1## wherein R.sup.1 is hydrogen or methyl, R.sup.2 is hydrogen or (E)-2-methyl 2-butenoyloxy, and R.sup.3 is hydrogen or hydroxy, with the proviso that when R.sup.3 is hydrogen, R.sup.1 and R.sup.2 are both hydrogen, and when R.sup.2 is (E)-2-methyl 2-butenoyloxy, R.sup.1 is methyl; the compound of formula (II): ##STR2## and the compound of formula (III): ##STR3## are obtainable by the fermentation of Streptomyces E225 NCIB 12310 or Streptomyces E225B NCIB 12509. The compounds have antihelminthic utility.

DETAILED DESCRIPTION We claim: 1.
A process for the production of a compound of formula (I) ##STR10## wherein R.
sup.
1 is hydrogen or methyl, R.
sup.
2 is hydrogen or E 2-methyl 2-butenoyloxy, and R.
sup.
3 is hydrogen or hydroxy, with the proviso that when R.
sup.
3 is hydrogen, R.
sup.
1 and R.
sup.
2 are both hydrogen, and when R.
sup.
2 is E 2-methyl 2-butenoyloxy, R.
sup.
1 is methyl, or a compound of formula (II) ##STR11## or a compound of formula (III) ##STR12## which process comprises cultivating a microorganism selected from the group consisting of Streptomyces E225, NCIB 12310, Streptomyces E225B, NCIB 12509, and any VM 44857, VM 44864, VM 44865, VM 44866, VM 44867, or VM 44868 producing mutant thereof, and recovering the desired compound of formula (I), (II), or (III).
2.
The process according to claim 1, for the production of a compound of formula (I), wherein R.
sup.
1, R.
sup.
2 and R.
sup.
3 are all hydrogen.
3.
The process of claim 1, wherein the microorganism is Streptomyces E225, NCIB 12310, or Streptomyces E225B, NCIB 12509.
4.
The process of claim 3, wherein the microorganism is Streptomyces E225, NCIB 12310.
5.
The process of claim 3, wherein the microorganism is Streptomyces E225B, NCIB 12509.




Description:
The present invention relates to novel anthelmintically active materials obtainable from a microorganism, to processes for their production, to pharmaceutical formulations containing them, and to their use in human or veterinary medicine.
A large number of microorganisms have been isolated, in particular from soil samples, and certain of those microorganisms have been found to produce various metabolites, which can be isolated and some of which have useful biological activity.
One group of such metabolites is the milbemycins, which have been prepared by the cultivation of microorganisms of the genus Streptomyces and are described in inter alia GB-A-1,390,336, J.
Antibiotics 29 (3), 76-14 to 76-16 and 29 (6), 76-35 to 76-42, U.
S.
Pat.
No.
4,144,352, and GB-A-2 056 986.
The



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