Total Synthesis of Two Isoflavone Bis-C-glycosides: Genistein and Orobol 6,8-Di-C-β-d-glucopyranosides

Abstract

This paper describes the first successful synthesis of two isoflavone bis-C-glycosides, genistein and orobol 6,8-di-C-β-d-glucopyranosides from phloroacetophenone bis-C-glycoside in total yields of 27 and 19%, respectively, using a four-step reaction: direct C-glycosylation of phloroacetophenone with unprotected d-glucose; chalcone synthesis by aldol condensation; acetal synthesis by oxidative rearrangement using DIB and p-TsOH; and formation of the isoflavone ring using HCl, without protection of the glucose moiety.

Key words

bis-C-glycoside - isoflavone - DIB - p-toluenesulfonic acid - oxidative rearrangement

References

• 1a Maurice J. C-Glycosylflavonoids, In The Flavonoids   Harborne JB. Chapman and Hall; London: 1994.  p.57-93  
• 1b Chopin J. Dellamonica G. C-Glycosylflavonoids, In The Flavonoids   Harborne JB. Chapman and Hall; London: 1988.  p.63-97  
• 2 Narayanan V. Seshadri TR. Indian J. Chem.  1971,  9:  14 
• 3 van Heerden FR. Brandt EV. Roux DG. J. Chem. Soc., Perkin Trans. 1  1980,  2463 
• 4 Nunes DS. Haag A. Bestmann HJ. Liebigs Ann. Chem.  1989,  4:  331 
• 5a Zavodnik LB. Zavodnik IB. Lapshina EA. Shkodich AP. Bryszewska M. Unko VU. Biochemistry (Moscow)  2000,  946 
• 5b Zavodnik LB. Radiat. Biol. Radioecol.  2003,  43:  432 
• 5c Kawaguchi K. Melloalves S. Watanabe T. Kikuchi S. Satake M. Kumazawa Y. Planta Med.  1998,  329:  855 
• 6a Matsubara Y. Suekuni H. Honda S. Kakehi K. Murakami T. Okamoto K. Miyake H. Jpn. Heart J.  1980,  21:  583 
• 6b Iizuka Y. Murakami T. Matsubara Y. Yokoi K. Okamoto K. Miyake H. Honda S. Kakehi K. Jpn. Heart J.  1980,  21:  584 
• 6c Kumamoto H. Matsubara Y. Iizuka Y. Okamoto K. Yokoi K. Agric. Biol. Chem.  1986,  50:  781 
• 6d Matsubara Y. Sawabe A. J. Synth. Org. Chem. Jpn.  1994,  52:  318 
• 6e Kawasaki M. Hayashi T. Arisawa M. Morita N. Berganza LH. Phytochemistry  1988,  27:  3709 
• 6f Ohsugi T. Nishida R. Fukami H. Agric. Biol. Chem.  1985,  49:  1897 
• 6g Basile A. Sorbo S. Lopez-Saez JA. Cobianchi RC. Phytochemistry  2003,  62:  1145 
• 7 Lee DYW. Zhang W.-Y. Karnati VVR. Tetrahedron Lett.  2003,  44:  6857 
• 8 Sato S. Hiroe K. Kumazawa T. Onodera J.-i. Carbohydr. Res.  2006,  341:  1091 
• 9 Sato S. Akiya T. Nishizawa H. Suzuki T. Carbohydr. Res.  2006,  341:  964 
• 10a Moriarty RM. Khosrowshahi JS. Prakash O. Tetrahedron Lett.  1985,  26:  2961 
• 10b Koser GF. Wetach RH. J. Org. Chem.  1976,  41:  3609 
• 10c Miki Y. Kobayashi S. Hachinken H. Synlett  1994,  1001 
• 10d Miki Y. Fujita R. Matsushita K. J. Chem. Soc., Perkin Trans. 1  1998,  2533 
• 10e Kawamura Y. Maruyama M. Tokuoka T. Tsukayama M. Synthesis  2002,  2490 
• 11a Wong E. The Flavonoids   Harborne JB. Marbry TJ. Mabry H. Chapman and Hall; London: 1975.  p.184 
• 11b Jain AC. Lal P. Seshadri TR. Indian J. Chem.  1969,  7:  305 
• 11c Hoshino Y. Miyaura N. Suzuki A. Bull. Chem. Soc. Jpn.  1988,  61:  3008 
• 12 Sato S. Akiya T. Suzuki T. Onodera J.-i. Carbohydr. Res.  2004,  339:  2611 

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These compounds were inseparable without AcOH in the solvent system owing to their instability.