J. Quintin, G. Lewin / Tetrahedron Letters 46(2005) 4341–4343
4343
1
case of the diosmin derivative 4, our method is a novel
chemical access to rutinose. As aforementioned,6 the
recovery of the intact sugar by alkaline hydrolysis was
not expected. However, addition of THF as cosolvent
in our procedure makes flavone 5 soluble at room tem-
perature ; so the very mild conditions of saponification
allow the recovery of rutinose in fair yield. Until now,
almost all the chemical synthesis of rutinose from a fla-
vonoid started from rutoside 16 (9–59% yields).12–17
saponification sequence; H and 13C NMR data of 4–
6, 9, 11, 12 and 15.
References and notes
1. Quintin, J.; Lewin, G. Tetrahedron Lett. 2004, 45, 3635–
3638.
2. Quintin, J.; Lewin, G. J. Nat. Prod. 2004, 67, 1624–1627.
3. Prepared from 1, 2 and 3 by a two-steps sequence (a)
Ac2O-pyridine, rt, 48 h; (b) TFA, rt, 6 h.
4. Kajigaeshi, S.; Kakinami, T.; Yamasaki, H.; Fujisaki, S.;
Kondo, M.; Okamoto, T. Chem. Lett. 1987, 2109–2112.
5. By comparison with an authentic sample from Extra-
OH
B
HO
O
OH
A
`
synthese.
rutinosyl
6. Reactivity of this intermediate depends on the structure of
the sugar and experimental conditions: sugars with a free
CH2OH at C-6 give as final compound a 1,6-anhydro
sugar by nucleophilic attack of the 1,2-epoxy system; in
the absence of this free CH2OH, the reaction leads to
methyl glycoside in MeONa–MeOH by nucleophilic
attack at C-1, and to tars in hot aqueous alkaline medium
by degradation of the sugar. In any case, the intact sugar is
not recovered at the end of the reaction.
7. Ballou, C. E. Adv. Carbohydr. Chem. 1954, 9, 59–95.
8. Nath, R. L.; Rydon, H. N. Biochem. J. 1954, 57, 1–10.
9. Wagner, G.; Nunh, P. Pharmazie 1966, 21, 205–214.
10. Koehler, L. H.; Hudson, C. S. J. Am. Chem. Soc. 1950, 72,
981–983.
O
OH
16
The best result was obtained by cleavage of the rutino-
syl–aglycon bond with dihalomethyl methyl ethers, but
this procedure was not at all selective with diosmin,
which gave mainly a rhamnose derivative.14 So, our
method uses the readily available diosmin as a raw
material for production of rutinose.
11. Litvinenko, V. I.; Makarov, V. A. Khim. Prir. Soedin.
1969, 5, 366–369.
Acknowledgement
´
12. Zemplen, G.; Gerecs, A. Ber. 1938, 71B, 2520.
The authors are grateful to J.-C. Jullian for NMR
measurements.
13. Bognar, R.; Farkas Szabo, I.; Farkas, I.; Gross, H.
Carbohydr. Res. 1967, 5, 241–243.
14. Koeppen, B. H. Carbohydr. Res. 1969, 10, 105–112.
15. Looker, J. H.; Sozmen, M.; Kagal, S. A.; Meyerson, S.
Carbohydr. Res. 1970, 13, 179–183.
Supplementary data
16. Japanese Patent JP 50059313 1975; Chem. Abstr. 83,
131900.
17. Kim, Y. C.; Higuchi, R.; Komori, T. Liebigs Ann. Chem.
1992, 575–579.
Supplementary data associated with this article can be