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Synthesis of 2,11-bis(methylidene)spermine, a new inhibitor of spermine oxidase

Abstract

Earlier unknown 1,12-diamino-2,11-bis(methylidene)-4,9-diazadodecane, which may be considered as an enzyme-activated inhibitor of spermine oxidase, was synthesized in 6 steps starting from 2-chloromethyl-3-chloropropene-1 in a high yield. Application of newly synthesized spermine analogue for the inhibition of spermine oxidase was discussed.

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Abbreviations

APAO:

acetylpolyamine oxidase

2,11-bis(methylidene)-Spm:

1,12-diamino-2,11-bis(methylidene)-4,9-diazadodecane

LSD1:

lysine specific demethylase

Ms:

methanesulfonyl

Ns:

o-nitrophenylsulfonyl

Put:

putrescine (1,4-diaminobutane)

SMO:

spermine oxidase

Spd:

spermidine (1,8diamino-4-azaoctane)

α-MeSpd:

(1,8-diamino-5-azanonane)

β-MeSpd:

(1,8-diamino-2-methyl-4-azaoctane)

Spm:

spermine (1,12-diamino-4,9-diazadodecane)

α,α'Me2Spm:

2,13-diamino-5,10-diazatetradecane

β,β'-Me2Spm:

1,12-diamino-2,11-dimethyl-4,9-diazadodecane

SSAT:

spermidine/spermine N 1-acetyltransferase

Pht:

phtaloyl

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Correspondence to A. R. Khomutov.

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Original Russian Text © N.A. Grigorenko, M.A. Khomutov, A.R. Simonian, S.N. Kochetkov, A.R. Khomutov, 2016, published in Bioorganicheskaya Khimiya, 2016, Vol. 42, No. 4, pp. 469–474.

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Grigorenko, N.A., Khomutov, M.A., Simonian, A.R. et al. Synthesis of 2,11-bis(methylidene)spermine, a new inhibitor of spermine oxidase. Russ J Bioorg Chem 42, 423–427 (2016). https://doi.org/10.1134/S1068162016030080

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  • DOI: https://doi.org/10.1134/S1068162016030080

Keywords

  • inhibitors
  • polyamines
  • spermine analogues
  • spermine oxidase