Nov., 1949
COMMUNICATIONS TO THE EDITOR
While folinic acid accounts for the major portion of the activity of extracts of hog liver, another factor with similar physical and biological properties occurs in these extracts. At least two other substances possessing activity in the assay have been detected by means of paper chromatography. Consequently, it appears that a group of compounds, the folinic acid group, possess activity similar to that of folinic acid. Since the folinic acid group is utilized more effectively than folic acid for several organisms, the possibility exists that it may be more active than folic acid in the treatment of sprue, nutritional and pernicious anemia, and other nutritional deficiencies related to the folic acid and vitamin BIZ groups.
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a lactal ring. Lactal ring opening by phenylhydrazone formation usually unmasks a hydroxyl group and the conversion of patulin phenylhydrazone (IV, R = H) by treatment with sodium
acetate-acetic anhydride to patulin phenylhydrazone acetate (IV, R = Ac), m. p. 143' (calcd. for CI5Hl4O4N2:C, 63.00; H , 4.93. Found: C, 63.40; H, 5.27) fits this interpretation. Infrared spectra of patulin phenylhydrazone ( 5 . 8 6 ~6.04p, ~ THE BIOCHEMICAL INSTITUTE AND THE THOMAS J. BOND 6 . 2 3 ~ )and its acetate ( 5 . 8 4 ~G.OOp, ~ 6 . 2 2 ~ )indiDEPARTMENT OF CHEMISTRY, THE THOMAS J. BARDOS cate retention of the doubly-unsaturated lactone OF TEXAS,AND THE MARGARET SIBLEY UNIVERSITY CLAYTON FOUNDATION FOR WILLIAMSHIVE system in these derivatives. Demonstration of a lactone ring in the phenylhydrazone and its aceRESEARCH, AUSTIN,TEXAS tate is shown by consumption of 1.05 and 1.92 RECEIVED SEPTEMBER 23, 1949 equivalents, respectively, of sodium hydroxide. Dihydropatulin (VI X = OH) phenylhydra~one~ THE STRUCTURE OF PATULIN contains only a singly-unsaturated lactone system Sir : (u.v., 380 mp, log E 4.55; 1.07 equivalents sodium Recent evidence has required revision of the ac- hydroxide). cepted structure (I)' of the antibiotic mold metabTreatment of patulin with warm excess thionyl olite, patulin, and two new formulations, (11)2and chloride followed by sublimation furnishes un(111, X = OH),3 have been advanced. The fol- stable patulyl chloride (111, X = C1) in 78yo lowing data now afford additional strong support yield, m. p. 92-94' (calcd. for C~H50&1: C, for (111, X = OH) as the structure of patulin. 48.70; HI 2.92; C1, 20.55. Found: C, 48.94; 0 H, 2.63; C1, 20.43); structural evidence given above. Patulyl chloride in anhydrous dioxane 0 0 with palladium-barium sulfate catalyst absorbs 2.0 of moles hydrogen in two hours to give a neutral fraction which furnishes on distillation oily diO 1 o'\o ' 0 \x (111) hydrodesoxypatulin (V, X = H) in 34% yield, b. p. 90-95' (0.5 mm.), (Calcd. for CvHs03: (11) 0 (1) sapon. equiv. 140.1. Found: 141.2); immediate Structure (111, X = OH) possesses three struc- Legal test; u.v., a t 212 mp, log E 3.93; ir., 5.57p, tural characteristics : free hydroxyl group, lactal 6 . 0 1 ~ . Accordingly, dihydrodesoxypatulin conring and doubly-unsaturated lactone system. tains a P,y-unsaturated-y-lactone system and its Presence of a free 0-H band (2.73p), in the infra- exact structure is established by hydrolysis in red spectrum of patulin and its absence in patulyl aqueous alcoholic sodium hydroxide to dihydroacetate (111, X = OAc) and in patulyl chloride desoxypatulinic acid (VI), identified by its well(111, X = Cl), retention of the characteristic known derivative^^^^^^^^ : 2,4-dinitrophenylhydradouble bond ultraviolet and infrared spectra of zone, m. p. 193-195'; methyl ester 2,d-dinitropatulin in these derivatives (Patulin: u.v., 275 phenylhydrazone, m. p. and m. m. p. 149-150' mp, log E 4.22; ir., 5.5814 5.9414 6.11,~. Acetate: (calcd. for C14H1607N4: C, 47.70; H, 4.58. u.v., 277 mp, log E 4.24; ir., 5.58p, 5 . 9 3 ~6.11~. ~ Found : C, 47.50; H, 5.02) ; p-phenylphenacyl Chloride: u.v., 277 mp, log E 4.18; ir., 5 . 6 1 ~ ~ester, m. p. 124-127'. 5.94~,6 . 1 3 ~ and ) ~ conversion of each in high yield DEPARTMENT OF CHEMISTRY AND CHEMICAL EXGINEERING to patulin phenylhydrazone by aqueous phenyl- UNIVERSITY OF WASHINGTON HYPJ . DAUBEN, JR. 5, WASHINGTON FRANKL.WEISENBORN hydrazine indicate the presence of a non-enolic SEATTLE RECEIVED SEPTEMBER 9, 1949 hydroxyl group and exclude occurrence of enoliza(4) Bergel, Morrison, Moss and Rinderknecht, J . Chem. Soc., 415 tion or isomerization during their preparation. Patulin shows reactions (negative Schiff, posi- (1944). are made gratefully t o Professor Raistrick tive Tollens, positive Fehling) characteristic of and(5)theAcknowledgments Therapeutic Research Corporation of Great Britain for the
bo Y (y)=o
ii;
(1) Birkinshaw, Bracken, Michael and Raistrick, Lancet, 245, 625 (1943); cf. Quart. Revs. Chcm. Soc., 4, 53 (1948). (2) Engel, Brzecki and Plattner, Hclu. Chim. Acta, 82, 1166, 1762 (1949). (8) Woodward and Sinsh, THID JOV~?IA&, 71, 768 (1949).
supply of patulin, t o Professor Woodward and Dr. Singh for helpful discussions, spectral determinations on the phenylhydrazone de. rivatives and an authentic sample of the methyl ester dinitrophenylhydrazone, and to E. I. du Pont de Namours end CB. to? tB%P ~ l f 9 w @hip# r a Q t d *SI RQe 9f HE (Ru t,w.).
