2974
C O M M U N I C A T I O N S T O THE E D I T O R
Vol. 82
Structure proof was provided by converting 11‘ to :3,20-diketo-l-pregnen-lS-oic acid (V) by hj-drolysis in C ; O ~ o sulfuric acid. X base-soluble product thus obtained was identical in melting point, paper-chromatographic migration rate and infrared spectrum with a genuine sample obtained from conessine.
exhibited by isoprene,5 a close model for the unsaturated portion of 11. Finally, the C-methyl group designated as (e) is split, as required, by the methine hydrogen at position 2 ; structure I , on the other hand, bears a methyl group in the ethyl unit, and would have given rise to a triplet in (e). The ultraviolet spectrum ( A % F 232 and 201 (4) R. Pappo, THIS J O U R N A L , 81, 1011 (1939). We wish to thank Dr. P a p p o for his kindness in providing us with t h e comparison sample. mp, E 23,100 and 790)’ and infrared absorption A. L. NUSSBALW an solution (inter alia, 5.8 p , ketone -CO-; 5.9 1-1, SCFIERINC CORPOR.4TION F. E. CARLOS imide -CO-; 6.0 (w) and 6.1 (w),diene)’ are E. P. OLIVETO consistent with the revised structure, 11. This RI.OOMFIEI.D, SEW JERSEY E. TOWNLEY formula is also compatible with the recoided cherniP. KABASAKALIAN R E S E a R C H I N S T I T U T E FOR M E D I C I N E cal and has been confirmed by addiA N D CHEMISTRY D. H. R. BARTOX tional chemical findings obtained more recently 49 AMHERSTSTREET in the laboratories of the Research Division of C A M R R I D G E , MASSACHUSETTS Parke, Davis and Company.’ RECEIVED APRIL 29, 1960 ( 5 ) Pople, Schneider and Bernstein, ibid., p. 244. ( 6 j T h e positive m-phenylenediamine test for a n 4 - u n s a t u r a t e d
STRUCTURE OF T H E ANTIBIOTIC STREPTIMIDONE
Sir: Recently structure I was proposed for a new CHa
CHZ
!i
C2H~-~=CIr-C-CO-CH1CHOHCH1c~
/cn2-Co \
YH
\ I CH*-CO Streptomyces antibiotic, streptimidone.’ It appeared to us that certain of the recorded properties, in particular the base-catalyzed conversion of the existing chromophore to a 2,4-dienone system, could be better interpreted in terms of an alternative, 11. We have now found that, by employing CH,
CHB
I
I
/CH2-Y 7”
ketone is regarded as due t o either prior isomerization of I1 t o a conjugated ketone system, or t o dehydration of t h e aldol moiety. ( 7 ) Re-examination of the ozonolysis of streptimidone has revealed t h a t formaldehyde and pyruvaldehyde are t h e end products, not formaldehyde and methyl ethyl ketone a s reported previously (ref. 1). T h e latter ketone originated a s a n impurity in t h e reagent ethyl acetate (distilled from 2,4-dinitrophenylhydrazine)vvhich was used a s a solvent in the isolation procedure (personal communication from H. 1x7. Dion. Parke, Davis and Company).
DEPARTMENT OF CHEMISTRY UNIVERSITY OF IVISCONSIN E. E. \’AX TAMELEN MADISON, Wrscoss~x 1’. HAARSTAD RECEIVED APRIL 8, 1960 ANTIPARASITIC DRUGS. 111. THIAMINEREVERSIBLE COCCIDIOSTATS
Sir : We have found that many 1-(2-alkyl-4-ainino-5-
pyrimidinylmethy1)-alkylpyridinium salts possess
CHFCH-C=CHCHCOCH~CHOHCH~CH
marked prophylactic activity in coccidiosis, a protozoan disease of importance in poultry production. I1 ‘CHz-CO -4nalogous 3-thiazoliumcompounds are also eff ective. nuclear magnetic resonance data, a clear decision The new anticoccidial agents are related strucin favor of the latter possibility can be made. turally to thiamine (11: R’ and R?, CHa, K 3 , The n.m.r. spectrum2 of 0-a~etylstreptimidone~CH2CH20H) and function by a reversible thiamine displays the following major absorptions, due to inhibition mechanism. These quaternaries, adhydrogens of the type indicated: (a) - 106 (imide) ; ministered in feed, are selectively effective against ( b ) ca. - 25 to +75 (olefinic, and acetoxyl methine) ; coccidia of the digestive tract and make possible (c) ca. $100 to $175 (saturated methine and adequate disease prevention without adverse effect methylene); (d) +178 and +186 (4- and acetyl upon the growth of chickens. Another relative of methyls), (e) +214 (2-methyl). The hydrogen the new coccidiostats is the thiamine antagonist peak ratio (1 : 5 ) of (a) to (b) supports formulation pyrithiamine (neopyrithiamine, I : R1and R2,CHs, 11, but not I. Furthermore, proposal I predicts R3, C H ~ C H Z O H ) . ~ essentially a simple three peak pattern in region Compounds of types I and I1 are made by reac(b), whereas that area features in fact an irregular tion of 2-alkyl-4-arnino-5-pyrimidinylmethyl halide quadruplet centered a t about 0 (one hydrogen), and broadened doublets a t about +45 and +62 (four hydrogens). This absorption character corU-i $-R2 responds to a superimposition of an “AB” (2)
