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Novel convenient synthesis of biologically active esters of hydroxylamine

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Abstract

Alkylation of ethyl N-hydroxyacetimidate with readily available methanesulfonates of functionally substituted alcohols and subsequent deprotection of aminooxy group is a novel and convenient method to prepare functionally substituted esters of hydroxylamine with high overall yield. This approach is a good alternative to well-known reaction of N-hydroxyphthalimide with alcohols under the Mitsunobu conditions. The properties of ethoxyethylidene protection of aminooxy group on the contrary to that of N-alkoxyphthalimide group allow to perform a wide spectra of the transformations in the radical of N-protected hydroxylamine derivatives. This is essential for synthetic strategies consisting in the introduction of N-protected aminooxy group at one of the first steps of synthesis and subsequent transformations of the radical.

The inhibitory effect of one of the newly synthesized compound, 1-guanidinooxy-3-aminopropane (GAPA), was compared with that of well-known inhibitors of ornithine decarboxylase namely, α-difluoromethylornithine (DFMO) and 1-aminooxy-3-aminopropane (APA) on Leishmania donovani, a protozoan parasite that causes visceral leishmaniasis. GAPA, on the contrary with APA and DFMO, in micromolar concentrations, inhibited the growth of both amastigotes and promastigotes of sodium antimony gluconate-resistant forms of L. donovani.

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Scheme 1
Scheme 2
Fig. 1

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Abbreviations

AdoMet:

S-Adenosylmethionine

Agm:

Agmatine (1-guanidino-4-aminobutane)

APA:

1-Aminooxy-3-aminopropane

DFMO:

α-Difluoromethylornithine

GAPA:

1-Guanidinooxy-3-aminopropane

Put:

Putrescine (1,4-diaminobutane)

Spd:

Spermidine (1,8-diamino-4-azaoctane)

SAG:

Sodium stibogluconate

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Acknowledgments

This work was supported by the Russian Foundation for Basic Research (project nos. 09-04-01272, 08-04-91317, and 08-04-91777), the program Molecular and Cell Biology of the Presidium of the Russian Academy of Sciences, grant from the Academy of Finland (project no. 124185), grant from the Council of Scientific and Industrial Research (CSIR), Government of India, and joint Indo-Russian DST-RFBR grant (project no. RUSP-883).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

    Maxim A. Khomutov, Alina R. Simonian & Sergey N. Kochetkov

  2. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India

    Swati Mandal, Neiha Saxena & Rentala Madhubala

  3. Department of Biosciences, Biocenter Kuopio, University of Kuopio, Kuopio, Finland

    Janne Weisell & Jouko Vepsalainen

Authors
  1. Maxim A. Khomutov
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  2. Swati Mandal
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  3. Janne Weisell
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  4. Neiha Saxena
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  5. Alina R. Simonian
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  6. Jouko Vepsalainen
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  7. Rentala Madhubala
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  8. Sergey N. Kochetkov
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Corresponding author

Correspondence to Maxim A. Khomutov.

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M. A. Khomutov, S. Mandal, and J. Weisell equally contributed to this work.

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Khomutov, M.A., Mandal, S., Weisell, J. et al. Novel convenient synthesis of biologically active esters of hydroxylamine. Amino Acids 38, 509–517 (2010). https://doi.org/10.1007/s00726-009-0410-0

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