LETTER
Synthesis of 2-Aryl Polyhydroxylated Pyrrolidines
1615
Kodzhimatov, O. K.; Ashurmetov, O. J. Nat. Med. 2008, 62,
236.
Finally, it is worth mentioning that treatment of highly ac-
tive phloroglucinol 9k with nitrones 6–8 in diluted reac-
tion solution at 0 °C afforded [1+1] adducts as major
products (dr = 99:1, Table 1, entries 16–18). Treatment of
1 equivalent of phloroglucinol 9k with 2 equivalents of ni-
trone resulted in the formation of [1+2] adducts, that is,
the 2,4-disubstituted phloroglucinols 40 and 41 as the ma-
jor products, with only a trace amount of the correspond-
ing [1+3] adducts being detected (Scheme 1).
(3) (a) Wang, C. L. J.; Calabrese, J. C. J. Org. Chem. 1991, 56,
4341. (b) Yoda, H.; Nakajima, T.; Takabe, K. Tetrahedron
Lett. 1996, 37, 5531. (c) Oliveira, D. F.; Severino, E. A.;
Correia, C. R. D. Tetrahedron Lett. 1999, 40, 2083.
(d) Severino, E. A.; Correia, C. R. D. Org. Lett. 2000, 2,
3039. (e) Haddad, M.; Larcheveque, M. Synlett 2003, 274.
(f) Chandrasekhar, S.; Jagadeshwar, V.; Prakash, S. J.
Tetrahedron Lett. 2005, 46, 3127. (g) Chowdhury, M. A.;
Reissig, H. U. Synlett 2006, 2383. (h) Chandrasekhar, S.;
Saritha, B.; Jagadeshwar, V.; Prakash, S. J. Tetrahedron:
Asymmetry 2006, 17, 1380. (i) Reddy, J. S.; Rao, B. V.
J. Org. Chem. 2007, 72, 2224. (j) Zhou, X.; Liu, W. J.; Ye,
J. L.; Huang, P. Q. Tetrahedron 2007, 63, 6346. (k) Ribes,
C.; Falomir, E.; Carda, M.; Marco, J. A. J. Org. Chem. 2008,
73, 7779. (l) Goti, A.; Cicchi, S.; Mannucci, V.; Cardona, F.;
Guarna, F.; Merino, P.; Tejero, T. Org. Lett. 2003, 5, 4235.
(m) Yu, C. Y.; Huang, M. H. Org. Lett. 2006, 8, 3021.
(n) Gurjar, M. K.; Borhade, R. G.; Puranik, V. G.; Ramana,
C. V. Tetrahedron Lett. 2006, 47, 6979. (o) Merino, P.;
Delso, I.; Tejero, T.; Cardona, F.; Goti, A. Synlett 2007,
2651. (p) Merino, P.; Delso, I.; Tejero, T.; Cardona, F.;
Marradi, M.; Faggi, E.; Parmeggiani, C.; Goti, A. Eur. J.
Org. Chem. 2008, 2929.
HO
OH
O–
N+
OH
HO
BnO
1) 9k (1 equiv),
AcCl, MeOH,
83–87%
H
N
H
N
2) Pd/C, H2,
93–94%
OH
HO
OH
BnO
OBn
HO
OH
(2 equiv)
40
6
HO
OH
O–
N+
1) 9k (1 equiv),
AcCl, MeOH,
83–87%
H
H
N
N
2) Pd/C, H2,
93–94%
OH
HO
OH
BnO
OBn
HO
OH
41
(2 equiv)
7
(4) (a) Schramm, V. L.; Tyler, P. C. Curr. Top. Med. Chem.
2003, 3, 525. (b) Merino, P.; Tejero, T.; Delso, I. Curr. Med.
Chem. 2008, 15, 954. (c) Kini, G. D.; Hennen, W. J.;
Robins, R. K. J. Org. Chem. 1986, 51, 4436.
Scheme 1 The synthesis of 2,4-disubstituted phloroglucinols
In summary, the Brønsted acid promoted F–C reaction of
polyhydroxylated cyclic nitrones with electron-rich aro-
matic compounds is an efficient method for the rapid syn-
thesis of the 2-aryl iminosugars. The method is capable of
diversity-oriented synthesis of compound library of 2-aryl
iminosugars, which is essential for the structure–activity
study of this special class of iminosugars.
(d) Horenstein, B. A.; Zabinski, R. F.; Schramm, V. L.
Tetrahedron Lett. 1993, 34, 7213. (e) Holzapfel, C. W.;
Crous, R. Heterocycles 1998, 48, 1337. (f) Momotake, A.;
Mito, J.; Yamaguchi, K.; Togo, H.; Yokoyama, M. J. Org.
Chem. 1998, 63, 7207. (g) Moreno-Vargas, A. J.; Carmona,
A. T.; Mora, F.; Vogel, P.; Robina, I. Chem. Commun. 2005,
4949. (h) Moreno-Clavijo, E.; Carmona, A. T.; Vera-Ayoso,
Y.; Moreno-Vargas, A. J.; Bello, C.; Vogel, P.; Robina, I.
Org. Biomol. Chem. 2009, 7, 1192. (i) Robina, I.; Moreno-
Vargas, A. J.; Fernandez-Bolanos, J. G.; Fuentes, J.;
Demange, R.; Vogel, P. Bioorg. Med. Chem. Lett. 2001, 11,
2555. (j) Moreno-Vargas, A. J.; Demange, R.; Fuentes, J.;
Robina, I.; Vogel, P. Bioorg. Med. Chem. Lett. 2002, 12,
2335. (k) Moreno-Vargas, A. J.; Robina, I.; Demange, R.;
Vogel, P. Helv. Chim. Acta 2003, 86, 1894. (l) Momotake,
A.; Togo, H.; Yokoyama, M. J. Chem. Soc., Perkin Trans. 1
1999, 1193. (m) Furneaux, R. H.; Limberg, G.; Tyler, P. C.;
Schramm, V. L. Tetrahedron 1997, 53, 2915. (n) Furneaux,
R. H.; Schramm, V. L.; Tyler, P. C. Bioorg. Med. Chem.
1999, 7, 2599. (o) Palmer, A. M.; Jager, V. Eur. J. Org.
Chem. 2001, 1293. (p) Severino, E. A.; Costenaro, E. R.;
Garcia, A. L. L.; Correia, C. R. D. Org. Lett. 2003, 5, 305.
(q) Tsou, E. L.; Chen, S. Y.; Yang, M. H.; Wang, S. C.;
Cheng, T. R. R.; Cheng, W. C. Bioorg. Med. Chem. 2008,
16, 10198. (r) Yokoyama, M.; Ikenogami, T.; Togo, H.
J. Chem. Soc., Perkin Trans. 1 2000, 2067. (s)Evans, G. B.;
Furneaux, R. H.; Gainsford, G. J.; Schramm, V. L.; Tyler,
P. C. Tetrahedron 2000, 56, 3053.
Supporting Information for this article is available online at
Acknowledgment
This work is supported by The National Natural Science Foundation
of China (No. 20672117), The National Basic Research Program of
China (No. 2009CB526511), The Ministry of Science and Techno-
logy and the Ministry of Health of the P. R. of China (No.
2009ZX09501-006), and The Chinese Academy of Sciences.
References and Notes
(1) (a) Stütz, A. E. Iminosugars as Glycosidase Inhibitors:
Nojirimycin and Beyond; Wiley-VCH: Weinheim: New
York, 1999. (b) Compain, P.; Martin, O. Iminosugars: From
Synthesis to Therapeutic Applications; John Wiley and
Sons: New York, 2007. (c) Watson, A. A.; Fleet, G. W. J.;
Asano, N.; Molyneux, R. J.; Nash, R. J. Phytochemistry
2001, 56, 265. (d) Asano, N.; Nash, R. J.; Molyneux, R. J.;
Fleet, G. W. J. Tetrahedron: Asymmetry 2000, 11, 1645.
(2) (a) Matkhalikova, S. F.; Malikov, V. M.; Yunusov, S. Y.
Khim. Prir. Soedin. 1969, 5, 30. (b) Shibano, M.;
(5) For review, see: Revuelta, J.; Cicchi, S.; Goti, A.; Brandi, A.
Synthesis 2007, 485.
(6) (a) Pellissier, H. Tetrahedron 2007, 63, 3235. (b) Brandi,
A.; Cicchi, S.; Cordero, F. M.; Goti, A. Chem. Rev. 2003,
103, 1213. (c) Gothelf, K. V.; Jørgensen, K. A. Chem. Rev.
1998, 98, 863.
(7) (a) Vilaivan, T.; Bhanthumnavin, W.; Sritana-Anant, Y.
Curr. Org. Chem. 2005, 9, 1315. (b) Lombardo, M.;
Trombini, C. Synthesis 2000, 759. (c) Merino, P. Nitrones
and Cyclic Analogues, In Science of Synthesis, 27; Padwa,
Tsukamoto, D.; Kusano, G. Heterocycles 2002, 57, 1539.
(c) Shibano, M.; Tsukamoto, D.; Masuda, A.; Tanaka, Y.;
Kusano, G. Chem. Pharm. Bull. 2001, 49, 1362. (d) Ishida,
S.; Okasaka, M.; Ramos, F.; Kashiwada, Y.; Takaishi, Y.;
Synlett 2010, No. 11, 1609–1616 © Thieme Stuttgart · New York