450 Proc. Japan Acad., 46 (1970) [Vol. 46,

106. Synthesis of Substances Related to Gibberellins. XXIII of (±)•Epiallogibberic Acid Biochemical Studies on "Bakanae" Fungus, Part 81*)

By Kenji MORI,Masanao MATSUI,and Yusuke SUMIKI Department of Agricultural Chemistry,University of Tokyo (Comm.by Teijiro YABUTA,M. J. A., May 12, 1970)

(+ ) -Epiallogibberic acid (I) , which contains the characteristic C/D ring system of gibberellic acid (II) , was first obtained as a degradation product of gibberellic acidly and later isolated as a meta- bolite of Gibberella f ujikuroi.2> After the completion of the total synthesis of some (±) -7-deoxygibberellins,3~ we turned our attention to the synthesis of this tetracyclic acid. Although the successful construction of its C/D ring system was carried out by three independent groups employing appropriate model compounds,4~-6 none of them has achieved a total synthesis of epi- allogibberic acid (I) or related natural products. Very recently, however, we devised a new method for the C/D ring construction and synthesized (-) -epiallogibberic acid (antipode of I) ?) starting from the known keto acid (IIIa) .8) This paper describes a formal total synthesis of (±) -epiallogibberic acid (I). The known keto diester (IV) ~~ was converted into (±) -7-de- methylepigibberic acid (XIa) in the same manner as reported for the synthesis of (±) -epigibberic acid (XIa, C-7 Me, instead of H) 1O),11) The Robinson annelation of the (IV) with methyl vinyl ketone gave a diacid (V), m.p. 243-244°, vmax ( Nuj ol) 1730, 1700, 1650, 1630, 1610 cm-1. This traps-diacid was heated with acetic anhydride to yield the anhydride (VI), m.p. 212-213°, vmax ( Nuj ol) 1815, 1760, 1660, 1625 cm-1, of cis-diacid. Intramolecular acylation was effected with etherate in acetic acid to give a diketo acid (VIIa), m.p. 247--248°, vmax(Nujol) 1750, 1725, 1635, 1620, 1605 cm-1. The corresponding methyl (VIIb), m.p. 154455°, vmax ( Nuj ol) 1740 (sh), 1735, 1660, 1615 cm-1, was heated with ethylene glycol and p-toluenesulfonic acid in 1,2-dichloro- ethane to give a ketal (VIII), m.p.196-197°, vmax(Nujol) 1730, 1670, *> Part 80: Kenji MORI, Masanao MATSUI, and Yusuke SUMIKI: Synthe- sis of Substances Related to Gibberellins. XXII. A New Method for the Con- struction of a Bicyclo [3.2. 11 octane Ring System with a Bridgehead Hydroxyl Group-A Partial Synthesis of (-)-Epiallogibberic Acid. Tetrahedron Letters, p. 429 (1970). No. 5] Synthesis of Substances Related to Gibberellins. XXIII 451

1620, 1590 cm-'. This was hydrogenated over Raney nickel W-7 to afford a hydroxy ester (IX), m.p.113-114 °, vmax3600, 1740, 1600 cm-'. Chromic anhydride in oxidized the alcohol (IX) to yield a keto ester (X), m.p. 167-168°, vmax ( Nuj ol) 1740, 1705 cm-1. This gave the racemic tetracyclic acid (XIa), m.p. 234-236°, vmax ( Nuj of ) 1740, 1600 cm-1, upon Huang Minlon reduction. The corresponding methyl ester (XIb) in was oxidized with trifluoroperacetic acid to give a racemic lactonic ester ( XII) , m.p. 166-167°, vmax (CHC13) 1732, 1600 cm-', o (100 MHz, CDC13) 2.22 (3H, s), 3.53 (1H, s), 3.69 (3H, s), 4.85 (1H, br. s), 6.85-7.30 (3H, aromatic H) ppm, MS: m/e 300 (M+), 282, 268, 241, 240, 199, 181, 156. These spectroscopic properties were entirely identical with those of the optically active ( XII) , m.p. 164- 452 K. MORI,M. MATSUI,and Y. SUMIKI [Vol. 46,

166°, which was adopted as the relay compound and prepared from gibberellic acid (II) . Reduction of the optically active lactone (XII ) with lithium aluminum hydride yielded a triol (XIII) , m.p. 229_2300, vmax (Nujol) 3300, 1595 cm-1. This was oxidized with the Jones chromic acid and the product was purified by chromatography on silicic acid to give a dicarboxylic acid (XIV) 1)8) m.p. 260-263°, vmax ( Nuj ol) 3450, 1745, 1705, 1680 cm-1. Treatment of this trans-diacid (XIV) with boiling acetic anhydride' gave the anhydride (XV),1),8) m.p. 288290°, vmax ( Nuj ol) 1815, 1765, 1705 cm-1, of cis-diacid. Boiling benzyl alcohol converted the anhydride (XV) into a half ester (Tub), which gave a gummy diester (Tile), vmax(film) 1735, 1705 cm-1, by treatment with ethereal diazomethane. Removal of the benzyl protective group of IIIc by catalytic hydrogenation over palladium-charcoal in ethyl acetate yielded a semi-solid product which was purified by chromatography on silicic acid to give the pure half ester (IIIa),1),7),8) m.p. 246-247°, vmax (Nujol) 3350, 1745, 1690, 1595 cm-1. The IR spectrum of this material was completely super- imposable on that of the authentic keto acid (IIIa). The identity was also established by m.m.p., TLC and MS. This completed the total synthesis of (±) -epiallogibberic acid. It is also to be noted that the present work is the first conversion .of a gibbane compound (XIa) into a 7-hydroxygibbane (I). Acknowledgement. We are indebted to Kyowa Fermentation Industry Co, for the generous gift of gibberellic acid.

References 1) J. F. Grove, and T. P. C. Mulholland: J. Chem. Soc., p. 3007 (1960). 2) J. R. Hanson : Tetrahedron, 22, 701 (1966). 3) K. Mori, M. Shiozaki, N. Itaya, M. Matsui, and Y. Sumiki : Tetrahedron, 25, 1293 (1969). 4) G. Stork, S. Malhotra, H. Thompson, and M. Uchibayashi: J. Am. Chem. Soc., 87, 1148 (1965). 5) R. A. Bell, R. E. Ireland, and L. N. Mander: J. Org. Chem., 31, 2536(1966). 6) E. J. Corey, M. Narisada, T. Hiraoka, and R. A. Ellison : J. Am. Chem. Soc., 92, 397 (1970). 7) K. Mori, M. Matsui, and Y. Sumiki: Tetrahedron Letters, p. 429 (1970). 8) T. P. C. Mulholland : J. Chem. Soc., p. 2693 (1958). 9) K. Mori, M. Matsui, and Y. Sumiki : Agr. Biol. Chem., 27, 27 (1963). 10) : Ibid., 26, 783 (1962). 11) : Ibid., 27, 537 (1963).