Synthesis of Hypericin via Emodin Anthrone Derived from a Two-fold Diels-Alder Reaction of 1,4-Benzoquinone

The six-step synthesis of hypericin by the regioselective two-fold Diels-Alder reaction of 1,4-benzoquinone first with (1-methoxy-3-methylbuta-1,3-dienyloxy)trimethylsilane leading to 7-methyljuglone, and next with (1,3-dimethoxybuta-1,3-dienyloxy)trimethylsilane, to give emodin and its O-methylated derivative. The reduction of both compounds with tin(II) chloride in acidic media was accompanied by acid hydrolysis that produced emodin anthrone, whose oxidative dimerization with iron (III) chloride hydrate gave the bianthrone in high yield. The oxidation of the bianthrone in the presence of N-ethyldiisopropylamine gave protohypericin, which was converted into hypericin upon irradiation.

[1]  H. Brockmann,et al.  Über das Hypericin, den photodynamisch wirksamen Farbstoff aus Hypericum perforatum , 1939, Naturwissenschaften.

[2]  M. Gill,et al.  Pigments of fungi. Part 68. Synthesis and absolute configuration of thysanone , 2002 .

[3]  P. Graham,et al.  Discovery, total synthesis, HRV 3C-protease inhibitory activity, and structure-activity relationships of 2-methoxystypandrone and its analogues. , 2001, Bioorganic & medicinal chemistry letters.

[4]  E. Gruszecka-Kowalik,et al.  AN IMPROVED SYNTHESIS OF HYPERICIN AND RELATED COMPOUNDS , 2000 .

[5]  Falk,et al.  From the Photosensitizer Hypericin to the Photoreceptor Stentorin- The Chemistry of Phenanthroperylene Quinones. , 1999, Angewandte Chemie.

[6]  S. Hayashi,et al.  Importance of the Role of Secondary Orbital Interactions in the Diels‐ Alder Reaction. Regioselectivity in the Catalyzed and Uncatalyzed Reactions of Juglone and Aliphatic Dienes. , 1997 .

[7]  S. Hayashi,et al.  Importance of the role of secondary orbital interactions in theDiels–Alder reaction. Regioselectivity in the catalyzed anduncatalyzed reactions of juglone and aliphatic dienes , 1997 .

[8]  R. Schmidt,et al.  An Expedient and Efficient Synthesis of Naturally Occurring Hydroxy Substituted Anthraquinones. , 1994 .

[9]  H. Falk,et al.  The Synthesis of Hypericin by Oxidative Trimethylemodin Anthrone and Emodin Anthrone Dimerization: Isohypericin. , 1993 .

[10]  H. Falk,et al.  On the synthesis of hypericin by oxidative trimethylemodin anthrone and emodin anthrone dimerization: Isohypericin , 1992 .

[11]  H. Falk,et al.  A synthesis of emodin anthrone , 1991 .

[12]  T. J. Simpson,et al.  A convenient synthesis of isotopically labelled anthraquinones, chrysophanol, islandicin, and emodin. Incorporation of [methyl-2H3]chrysophanol into tajixanthone in Aspergillus variecolor , 1987 .

[13]  P. Song,et al.  HYPERICIN AND ITS PHOTODYNAMIC ACTION , 1986, Photochemistry and photobiology.

[14]  Jacques Savard,et al.  Reactions of ketene acetals-14 The use of simple mixed vinylketene acetals in the annulation of quinones , 1984 .

[15]  W. Steglich,et al.  Synthesis of Hypericin and Related meso‐Naphthodianthrones by Alkaline Dimerization of Hydroxyanthraquinones , 1977 .

[16]  D. Spitzner.  Synthesis of Protohypericin from Emodin , 1977 .

[17]  D. Cameron,et al.  Oxidation of emodin anthrone and stereochemistry of emodin bianthrone , 1976 .

[18]  W. Steglich,et al.  Alkaline condensation of emodin to isohypericin: a simple synthesis of the meso-naphthodianthrone (phenanthro(1,10,9,8-opqra)perylene) system. , 1973, Angewandte Chemie.

[19]  R. H. Thomson.  Naturally occurring quinones , 1957 .