T. Shinada et al. / Tetrahedron Letters 47 (2006) 1945–1947
1947
In summary, we developed a simple method to access N-
acyl-N -substituted guanidines from N-acylthioureas by
4. Bream, J. B.; Picard, C. W. Chem. Abstr. 1972, 76, 72286.
0
5
6
. Benos, D. J. Am. J. Physiol. Cell Physiol. 1982, 242, C131–
C145.
. Scholz, W.; Albus, U.; Counillon, L.; Gogelein, H.; Lang,
H.-J.; Linz, W.; Weichert, A.; Scholkens, B. A. Cardio-
vasc. Res. 1995, 29, 260.
the use of HMDS. Various N-acylguanidine derivatives
were prepared from the corresponding thioureas in a
facile manner. Application of this method for the syn-
thesis of biologically active guanidines and guanidine-
containing natural products is currently underway.
7
8
. Baumgarth, M.; Beier, N.; Gericke, R. J. Med. Chem.
1
997, 40, 2017.
. Ahmad, S.; Doweyko, L. M.; Dugar, S.; Grazier, N.; Ngu,
K.; Wu, S. C.; Yost, K. J.; Chen, B.-C.; Gougoutas, J. Z.;
DiMarco, J. D.; Lan, S.-J.; Gavin, B. J.; Chen, A. Y.;
Dorso, C. R.; Serafino, R.; Kirby, M.; Atwal, K. S. J.
Med. Chem. 2001, 44, 3302.
Acknowledgments
Financial support was provided by JSPS KAKENHI
9
. (a) Lee, S.; Yi, K. Y.; Hwang, S. K.; Lee, B. H.; Yoo, S.;
Lee, K. J. Med. Chem. 2005, 48, 2882; (b) Padmanabhan,
S.; Lavin, R. C.; Thakker, P. M.; Guo, J.; Zhang, L.;
Moore, D.; Perlman, M. E.; Kirk, C.; Daly, D.; Burke-
Howie, K. J.; Wolcott, T.; Chari, S.; Berlove, D.; Fischer,
J. B.; Holt, W. F.; Durant, G. J.; McBurney, R. N. Bioorg.
Med. Chem. Lett. 2001, 11, 3151.
(
Nos. 16201045 and 16073214).
References and notes
. (a) Masereel, B.; Pochet, L.; Laeckmann, D. Eur. J. Med.
1
Chem. 2003, 38, 547; (b) Peyman, A.; Scheunemann,
K.-H.; Will, D. W.; Knolle, J.; Wehner, V.; Breipohl, G.;
Stilz, H. U.; Carniato, D.; Ruxer, J.-M.; Gourvest, J.-F.;
Auberval, M.; Doucet, B.; Baron, R.; Gaillard, M.;
Gadek, T. R.; Bodary, S. Bioorg. Med. Chem. Lett.
10. (a) Kehraus, S.; Gorzalka, S.; Hallmen, C.; Iqbal, J.;
Muller, C. E.; Wright, A. D.; Wiese, M.; Konig, G. M. J.
Med. Chem. 2004, 47, 2243; (b) Wessels, M.; Konig, G.
M.; Wright, A. D. J. Nat. Prod. 2001, 64, 1556; (c)
Graziani, E. I.; Andersen, R. J. J. Nat. Prod. 1998, 61,
285.
2
001, 11, 2011; (c) Adang, A. E. P.; Lucas, H.; de Man, A.
P. A.; Engh, R. A.; Grootenhuis, P. D. J. Bioorg. Med.
Chem. Lett. 1998, 8, 3603; (d) Thomas, E. W.; Nishizawa,
E. E.; Zimmermann, D. C.; Williams, D. J. J. Med. Chem.
11. (a) Tsukamoto, S.; Kato, H.; Hirota, H.; Fusetani, N.
Tetrahedron Lett. 1996, 37, 5555; Structure revision, see:
(b) Nozawa, D.; Takikawa, H.; Mori, K. Bioorg. Med.
Chem. Lett. 2001, 11, 1481.
1
989, 32, 228.
2
3
. For reviews: (a) Saczewski, F. In Comprehensive Organic
Functional Group Transformations II; Katritzky, A. R.,
Taylor, R. J. K., Scriven, E. F. V., Eds.; Elsevier Ltd.:
Oxford, 2005; Vol. 6, Chapter 6.21; (b) Berlinck, R. G. S.
Nat. Prod. Rep. 2002, 119, 617; (c) Heys, L.; Moore, C. G.;
Murphy, P. J. Chem. Soc. Rev. 2000, 29, 57.
. Synthesis of N-acyl guanidines: (a) Katritzky, A. R.;
Rogovoy, B. V.; Cai, X.; Kirichenko, N.; Kovalenko, K.
V. J. Org. Chem. 2004, 69, 309; (b) Cunha, S.; de Lima, B.
R.; de Souza, A. R. Tetrahedron Lett. 2002, 43, 49; (c)
Zhang, J.; Shi, Y.; Stein, P.; Atwal, K.; Li, C. Tetrahedron
Lett. 2002, 43, 57; (d) Dodd, D. S.; Zhao, Y. Tetrahedron
Lett. 2001, 42, 1259; (e) Ghosh, A. K.; Hol, W. G. J.; Fan,
E. J. Org. Chem. 2001, 66, 2161; (f) Cunha, S.; Costa, M.
B.; Napolitano, H. B.; Lariucci, C.; Vencato, I. Tetra-
hedron 2001, 57, 1671; (g) Padmanabhan, S.; Lavin, R. C.;
Thakkar, P. M.; Durant, G. J. Synth. Commun. 2001, 31,
12. (a) Miyabe, H.; Matsumura, A.; Yoshida, K.; Yamauchi,
M.; Takemoto, Y. Lett. Org. Chem. 2004, 1, 119; (b)
Powell, D. A.; Ramsden, P. D.; Batey, R. A. J. Org. Chem.
2003, 68, 2300; (c) Baker, T. J.; Tomioka, M.; Goodman,
M. Org. Syn. 2002, 78, 91; (d) Dodd, D. S.; Kozikowski,
A. P. Tetrahedron Lett. 1994, 35, 977.
13. Citerio, L.; Rivera, E.; Saccarello, M.-L.; Stradi, R.;
Gioia, B. J. Heterocycl. Chem. 1980, 17, 97.
14. Goetz, N.; Zeeh, B. Synthesis 1976, 268.
15. (a) Greenhalgh, R.; Bannard, R. A. B. Can. J. Chem.
1961, 39, 1017; (b) Yamamoto, Y.; Kojima, S. In The
Chemistry of Amidines and Imidates; Patai, S., Rappoport,
Z., Eds.; John Wiley & Sons: New York, 1991; Vol. 2,
Chapter 10.
16. Typical procedure for the condensation reaction. To a
solution of 10a (314 mg, 1 mmol) and HMDS (2.09 mL,
10 mmol) in CH CN (10 mL) was added EDCI (383 mg,
3
2
9
491; (h) Lin, P.; Ganesan, A. Tetrahedron Lett. 1998, 39,
789; (i) Poss, M. A.; Iwanowicz, E.; Reid, J. A.-I.; Lin,
2 mmol) at 0 ꢁC with stirring. The mixture was stirred for
2 h, poured into water, and extracted with AcOEt
(50 mL · 2). The combined organic layers were dried over
R.; Gu, Z. Tetrahedron Lett. 1992, 33, 5933; (j) Okajima,
N.; Okada, Y. J. Heterocycl. Chem. 1991, 28, 177; (k)
Groziak, M. P.; Townsend, L. B. J. Org. Chem. 1986, 51,
anhydrous MgSO and filtered. The filtrate was concen-
4
trated under reduced pressure. The residue was purified by
flash column chromatography (AcOEt/hexane (1:4) to
1
277; (l) Augustin, M.; Richter, M.; Salas, S. J. Prakt.
Chem. 1980, 55; (m) Schaumann, E.; Kausch, E. Justus
Liebigs Ann. Chem. 1978, 1543; (n) Kantlehner, W.;
Funke, E.; Haug, E.; Speh, P.; Kienitz, L.; Maier, T.
Synthesis 1977, 73; (o) Matsuda, I.; Itoh, K.; Ishii, Y. J.
Organomet. Chem. 1974, 69, 353; (p) Bredereck, H.;
Simchen, G.; Porkert, H. Chem. Ber. 1970, 103, 245; (q)
Goerdeler, J.; Mertens, P. Chem. Ber. 1970, 103, 1805; (r)
Itoh, K.; Matsuda, I.; Ishii, Y. Tetrahedron Lett. 1969, 31,
AcOEt) to give 11a (271 mg, 92%) as colorless crystals.
1
Mp 194–196 ꢁC (MeOH). H NMR (400 MHz, CDCl
) d
3
8.17 (d, J = 6.6 Hz, 2H), 7.40–7.36 (m, 3H), 7.15 (br s,
1
3
1H), 2.10 (br s, 3H), 2.02 (br s, 6H), 1.67 (br s, 6H).
NMR (100 MHz, CDCl ) d 177.3, 160.7, 138.8, 130.8,
128.8, 127.8, 51.9, 42.2, 36.1, 29.3. HRMS (FAB ) calcd
C
3
+
+
23 3
for [C18H N O+H] 298.1919, found 298.1914.
17. Carbodiimide derivatives bearing an electron-withdrawing
group have been synthesized by dehydration reaction of
2
675; (s) Ito, G. Chem. Pharm. Bull. 1961, 9, 245; (t)
Johnson, T. B.; Chernoff, L. H. J. Am. Chem. Soc. 1912,
4, 164.
2
a,3k
urea derivatives using COCl
references cited in 2a and 3k.
2
and Et
3
N.
See also
3