Abstract
Aliphatic polyamines, being a versatile class of organic compounds, are widely used in many fields of medicine and organic chemistry. However, the general approach to the synthesis of chiral aliphatic polyamines has been still undeveloped. Here, we describe a new method for the synthesis of chiral trifunctional amino compounds, namely hydroxydiamines and triamines. The initial compounds, namely substituted hydroxy- or aminopyrazolidines and pyrazolines, are readily available using convenient stereoselective methods developed earlier by us. The proposed method allows synthesizing of chiral diaminoalcohols and triamines, which are the analogs of a well-known anti-TB drug, namely ethambutol, and cannot be obtained alternatively. The key step of the synthesis is N–N bond cleavage in substituted hydroxy- or aminopyrazolidines and pyrazolines with borane-tetrahydrofuran complex; other known methods for N–N bond cleavage turned out to be ineffective. The main advantage of the proposed method is the retention of a certain configuration of stereocenters in the course of the reaction. Six new chiral diasteomerically pure substituted hydroxydiamines and triamines and the enantiomerically pure triamine with four chiral centers were synthesized and characterized using NMR, IR and mass spectroscopy, as well as elemental analysis.
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Abbreviations
- Anti-TB drugs:
-
Antituberculosis drugs
- THF:
-
Tetrahydrofuran
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Acknowledgments
This research was supported partly by the Russian Academy of Sciences, grant P5 “Fundamental Sciences to Medicine,” grant no.10 “Biomolecular and Medical Chemistry” and the Russian Foundation for Basic Research (grant nos. 09-03-01097 and 11-04-01245).
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Sviridova, L.A., Golubeva, G.A., Tavtorkin, A.N. et al. Synthesis of hydroxydiamines and triamines via reductive cleavage of N–N bond in substituted pyrazolidines. Amino Acids 43, 1225–1231 (2012). https://doi.org/10.1007/s00726-011-1187-5
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DOI: https://doi.org/10.1007/s00726-011-1187-5