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Synthesis of 2-Methylidene Spermidine and its N1-Acetylated Derivative

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Abstract—

Simple and practical synthetic protocols have been developed for the preparation of earlier unknown 2-methylidene derivatives of spermidine and N1-Ас-spermidine, i.e., 1,8-diamino-2-methylidene-4-azaoctane (2-Met-Spd) and N1-(acetyl)-1,8-diamino-2-methylidene-4-azaoctane (N1-Ас-2-Met-Spd), respectively. Target compounds were obtained each in seven steps with high overall yields starting from the commercially available 2-chloromethyl-3-chloropropene-1. Possible application of newly synthesized spermidine analogs for the inhibition of FAD-dependent N1-acetyl polyamine oxidase is discussed.

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ACKNOWLEDGMENTS

The authors thank A.O. Chizhov (Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences) for recording mass spectra.

Funding

This study was supported by the Russian Foundation for Basic Research (project no. 17-74-20049).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    M. A. Khomutov & A. R. Khomutov

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  1. M. A. Khomutov
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  2. A. R. Khomutov
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Correspondence to M. A. Khomutov.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by M. Novikova

Abbreviations: dcAdoMet, S-adenosyl-L-methionine decarboxylase; ODC, ornithine decarboxylase; PAOX, N1-acetylpolyamine oxidase; 2-Met-Spd, 1,8-diamino-2-(methylidene)-4-azaoctane; N1-Ас-2-Met-Spd, N1-(acetyl)-1,8-diamino-2-(methylidene)-4-azaoctane; Spd, spermidine (1,8-diamino-4-azaoctane); Spm, spermine (1,12-diamino-4,9-diazododecane); SMOX, spermine oxidase; SSAT, spermidine/spermine N1-acetyltransferase; N1-Ас-Spd, N1-(acetyl)-1,8-diamino-4- azaoctane; N1-Ас-Spm, N1-(acetyl)-1,12-diamino-4,9-diazododecane.

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Khomutov, M.A., Khomutov, A.R. Synthesis of 2-Methylidene Spermidine and its N1-Acetylated Derivative. Russ J Bioorg Chem 48, 1202–1208 (2022). https://doi.org/10.1134/S1068162022060140

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