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HETEROCYCLES, Vol. 73, 2007
of active MenA inhibitors, we have demonstrated the syntheses of specific structure of hydrazine
derivatives as summarized in Table 2. However, tert-butyl 2-alkylhydrazinecarboxylates (i.e.
o
BocHNNHMe) were loaded onto the tetrachlorodiphenylmethoxycarbonyl linker at 50 C and the Boc
group could be removed selectively by using 15% TsOH•H2O in THF-CH2Cl2 (1/1).13 Thus, the method
described here may be applicable to the synthesis of 1,2-disubstituted and 1,1,2-trisubstituted hydrazine
derivatives in a high-throughput manner. Generation of library molecules using the hydrazine building
blocks synthesized by the described method and evaluation of these molecules against MenA and MDR
Gram-positive bacteria will be reported elsewhere.
ACKNOWLEDGEMENTS
We thank the National Institutes of Health (NIAID grants AI049151, AI018357, and AI06357) and
Colorado State University for generous financial support. Mass spectra were obtained on instruments
supported by the NIH Shared Instrumentation Grant GM49631.
REFERENCES AND NOTES
1. K. D. Suvana, R. Stevenson, R. Meganathan, and M. E. S. Hudspeth, J. Bacteriol., 1998, 180, 2782.
2. M. Kurosu and D. C. Crick, Compositions and Methods of Use of Electron Transport System
Inhibitors Serial Number: PCT / US2007 / 63122.
3. M. Kurosu, P. Narayanasamy, K. Biswas, R. Dhiman, and D. C. Crick, J. Med. Chem., 2007 in press.
4. For a recent report on the alkylation of protected hydrazines, see: L. K. Rasmussen, J. Org. Chem.,
2007, 71, 3627; J. Barluenga, P. Moriel, F. Aznar, and C. Valdés, Org. Lett., 2007, 9, 275 and
references therein. For a review, see: A. Zergra, Curr. Med. Chem., 2005, 12, 589.
5. N. Brosse, M. F. Pinto, J. Bodiguel, and B. Jamart-Grégorire, J. Org. Chem., 2001, 66, 2869; O.
Tśubrik and U. Mäeorg, Org. Lett., 2001, 3, 2297; N. Brosse, M. F. Pinto, and B. Jamart-Grégorire, J.
Org. Chem., 2000, 65, 4370; U. Mäeorg and U. Ragnarsson, Tetrahedron Lett., 1998, 39, 681.
6. A. Bredihhin, U. M. Groth, and U. Mäeorg, Org. Lett., 2007, 9, 1097.
7. N-Amination reactions have been widely demonstrated in the synthesis of 1,1-disubstituded
hydrazines, see: U. Ragnarson, Chem. Soc. Rev., 2001, 30, 205.
1
8. Data for 5a: H-NMR (CDCl3, 300 MHz): δ 7.55 (s, 1H), 7.37 (m, 1H), 7.26 (m, 2H), 6.88 (s, 2H),
6.34 (bs, 1H ), 6.31 (bs, 1H), 3.81 (s, 3H), 1.46 (s, 9H).; 13C-NMR (CDCl3, 100 MHz): 159.9, 155.3,
136.9, 130.5, 129.7, 126.5, 124.3, 115.3, 81.3, 72.4, 55.8, 28.1.; IR (neat, cm-1): 3583, 2919, 2362,
1652, 1558. LRMS (ESI) C20H21N2O5Cl4 (M+H+) 509.0.
9. Data for 6a: 1H-NMR (CDCl3, 300 MHz): δ 7.56 (s, 1H), 7.25 (m, 7H), 6.88 (s, 2H), 6.36 (bs, 1H ),