RAMACHANDRAN, CHEXG,AND HORTON
2744
VOL. 28
The Synthesis of Euparin and Dehydrotremetone P. K.
RA4MACHASDRAN, T. CHEKG, AND
w.J. HORTON
Department of Chemistry, University of Utah, Salt Lake City, Utah
Received April 16, 1963 Euparin (111) has been synthesized from methyl 5-acetyl-6-hydroxycoumarilate ( I ) via the 0-acetate, the ethylene ketal, and the readily dehydrated tertiary alcohol obtained by reaction of methylmagnesium iodide with the latter. Acetylation of methyl coumarilate gave methyl 5-acetylcoumarilate (IV) as shown by conversion to 5-ethylcoumarilic acid and independent synthesis of this latter compound. Dehydrotremetone (VII) was obtained by addition of methylmagnesium iodide to the ketal of IV followed by dehydration and removal of the ketal group.
The structure of euparin (111), a yellow substance from h'upatoriz'm purpureum, was determined by Kamthong and Robertson,' who isolated the material from the roots of the plant. It subsequently has been isolated from E . cannabinum2 and from E . japonica.3 In an investigation of the point of attack in the boron triquoride-catalyzed acetylation of isomeric methyl methoxycoumarilate~,~ it was found that methyl 6 methoxycoumarilate was acetylated a t 80" to yield methyl 5- and 7-acetyl-6- hydroxycoumarilates which could be conveniently separated by fractional crystallization. illilder conditions gave methyl 5- and 7acetyl-6-methoxycoumarilates which were not easily separable.
C H , - C w
a
C H , - C w
II
I, R = HO 11, R = CHaCO
II
IV, R
=
H
0 111, R VII, R
= =
HO H
0
The availakdity of I, therefore, suggested the preparation of euparin (111). The 0-acetate I1 formed a ketal with ethyiene glycol followed apparently by loss of the acetyl group, since attempts to form the ketal from I were not successful. The ketal with excess methylmagnesium iodide gave a tertiary alcohol which easily lost water to form the isopropylene group. Chromatography on acid washed alumina cleaved the ketal to produce euparin (111)directly. The ease of dehydration of the tertiary alcohol is in contrast to the more difficult dehydration of 2-(5'-acetyl-2',3'-dihydro-2/ben~ofuryl)-2-propanol.~ The synthet,ic euparin melted a t 121-122' and formed a semicarbaxone, a dinitrophenylhydrazone, and a maleic anhydride adduct all in agreement with the published The green color with ferric chloride and the color pattern with concentrated sulfuric acid were those reported.' J . Ckem. SOC..925 (1939). (2) F. v. Gizycki. Siiddeuf. Apofh.-Ztg.. 90, 503 (1950) [Chem. Abstr., 4 4 , 9118 (1950)l; (b) Z. I . Jerzmanowska, Polska Akad. Cmiejetnosci, Prace Komasja 4 a u k Farm. Dissertafiones Pkarm., 3, 165 (19.51) [Ckem. Abatr., 48, ,5848 (1934)]; (c) J . Sykulski, Acta Polon. Pkarm., 16, 361 (1958); [Chem. .45slr.. 63,8530 (19:g)I. (3) T . Nakaoki, S . Morita, and S. Nishino, Yakugaku Zasshi, 78, 567 (1958) [Chem. Abstr.. 62, 13190 (1958)l. (4) P. I
