4
Tetrahedron Letters
Table 3 Iodination of Protected Flavonoid Derivatives (Continued)
Entry
Substrates
Methoda
Iodinated products
Yieldb
74%
5
B
6
B
78%
aMethod A: reactions were preformed with substrate (1.0 mmol) and NIS (1.2 mmol) in DMF at rt; Method B: reactions were preformed with substrate (1.0
mmol) and NIS (1.2 mmol) in DMF at 70 oC; bIsolated yield after chromatography.
55, 2649-2652. (c) Park, H.; Dao, T. T.; Kim, H. P. Eur. J. Med.
Chem. 2005, 40, 943-948. (d) Zhang, F. J.; Li, Y. L. Synthesis
1993, 565-567. (e) Gurung, S.K.; Kim, H. P.; Park. H. Arch.
Conclusion
In summary, NIS in DMF was found to be an excellent
reagent for the regioselective synthesis of C-6 and C-8 monoiodo
flavonoids. The iodination can be conveniently directed to either
the C-6 or C-8 position by alternating the protection pattern on
the C-5 and C-7 OH groups. Thus, 5,7-O-dialkylated flavonoids
can be iodinated with NIS/DMF to give exclusively the 8-iodo
derivatives whereas alkyl ethers of flavonoids bearing a free OH
group at C-5 lead only to the 6-iodo products. The mild and
neutral conditions of this new iodination reaction proved to be
particularly useful for functionalization of acid-labile substrates
Pharm. Res. 2009, 32, 1503-1508.
12. Zheng, X.; Meng, W.-D.; Xu, Y.-Y.; Cao, J.-G.; Qing, F.-L.
Bioorg. Med. Chem. Lett. 2003, 13, 881-884.
13. (a) Quintin, J.; Lewin, G. Tetrahedron Lett. 2004, 45, 3635-3638;
(b) Quintin, J.; Lewin, Guy. J. Nat. Prod. 2004, 67, 1624-1627.
14. (a) Bovonsombat, P.; Leykajarakul, J.; Khan, C.; Pla-on, K.;
Krause, M. M.; Khanthapura, P.; Ali, R.; Doowa, N. Tetrahedron
Lett. 2009, 50, 2664–2667. (b) Castanet, A.-S.; Colobert, F.;
Broutin, P.-E. Tetrahedron Lett. 2002, 43, 5047–5048. (c) Heald,
R.A.; Dexheimer, T.S.; Vankayalapati, H.; Siddiqui-Jain, A.;
Szabo, L.S.; Gleason-Guzman, M.C. and Hurley, L.H. J. Med.
Chem. 2005, 48, 2993-3004. (d) Gautam, R.; Jachak, S. M.;
Kumar, V.; Mohan, C. G. Bioorg. Med. Chem. Lett. 2011, 21,
1612-1616.
15. General Procedure of Iodination Reactions: to a stirred solution of
5 (358 mg, 1.0 mmol) in dry DMF (4 mL) was added portionwise
NIS (270 mg, 1.2 mmol). After the addition, the mixture was
stirred for 10 h at room temperature. The reaction mixture was
then diluted with CH2Cl2 (20 mL) and poured into saturated
aqueous NaHCO3 (10 mL). The organic layer was separated,
washed with H2O (3×10 mL) and dried over Mg2SO4. After
concentrated to dryness under reduced pressure, the crude product
was purified by column chromatography on silica (petroleum
ether/ethyl acetate 3:1) to afford compound 6 (387 mg, 80%).
as exemplified by
a glycolated flavonoid. Halogenated
flavonoids are versatile compounds for the synthesis of novel
flavonoids and biflavonids. The convenient access to 6- and 8-
iodo flavonoids by using NIS/DMF helps open new doors for the
research of flavonoids. Further conversion to C-alkyl substituted
flavonoids, biflavonoids and their derivatives using the iodo
flavonoids as the key intermediates are underway in our
laboratory.
Acknowledgments
The authors sincerely thank the financial support from
National Science Foundation of China (Grants 21202118,
81241104) and The Ministry of Education Changjiang Scholars
and Innovative Research Team Development Plan (IRT1166).
Supplementary Material
Supplementary data (experimental procedures and analytical data
for all the new compounds) associated with this article can e
found, in the online version
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