- Practical synthesis of spermine, thermospermine and norspermine
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Polyamines, such as spermine (1), thermospermine (2) and norspermine (3), are widely distributed in nature, and have multiple biological activities. In addition, many of their conjugates have potential for pharmacological use. Here, we present a solid-phase synthesis using our nitrobenzenesulfonyl (Ns) strategy, which can provide 1, 2 and 3 on a gram scale. This approach should be suitable for facile construction of a diverse library of polyamines.
- Kariya, Yuka,Asanuma, Yuta,Inai, Makoto,Asakawa, Tomohiro,Ohashi-Ito, Kyoko,Fukuda, Hiroo,Egi, Masahiro,Kan, Toshiyuki
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p. 1403 - 1407
(2016/09/09)
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- Process for the preparation of N,N,N',N'-tetrakis(3-aminopropyl)-1,4-butanediamine
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The invention provides a process for the preparation of N,N,N',N'-tetrakis(3-aminopropyl)-1,4-butanediamine by hydrogenation of 3,3',3",3"'-(1,4-butanediyldinitrilo)tetrakispropanenitrile, wherein 3,3',3",3"'-(1,4-butanediyldinitrilo)tetrakispropanenitrile is continuously added to a suspension or solution of a catalyst in a solvent which optionally comprises one or more additives and is stirred at a temperature in the range from 40 to 150 °C under a hydrogen pressure, characterized in that (i) the solvent is tetrahydrofuran, (ii) the catalyst is a hydrogenation catalyst selected from the group consisting of (1) Sponge Metal Cobalt, A-8B46, promoted with Nickel and Chromium, (2) Raney Cobalt, 2724, promoted with Chromium, (3) Actimet Cobalt and (4) Activated Ni catalyst, B 113 W, and (iii) the hydrogen pressure is from 30 to 50 bar. This special combination of catalyst and solvent allows the preparation of N,N,N',N'-tetrakis(3-aminopropyl)-1,4-butanediamine in high purity under a moderate hydrogen pressure which is suitable for large scale synthesis.
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Paragraph 0022-0026
(2013/03/26)
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- Crystal structures and enzymatic properties of a triamine/agmatine aminopropyltransferase from thermus thermophilus
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To maintain functional conformations of DNA and RNA in high-temperature environments, an extremely thermophilic bacterium, Thermus thermophilus, employs a unique polyamine biosynthetic pathway and produces more than 16 types of polyamines. In the thermophile genome, only one spermidine synthase homolog (SpeE) was found and it was shown to be a key enzyme in the pathway. The catalytic assay of the purified enzyme revealed that it utilizes triamines (norspermidine and spermidine) and agmatine as acceptors in its aminopropyl transfer reaction; therefore, the enzyme was denoted as a triamine/agmatine aminopropyltransferase (TAAPT). We determined the crystal structures of the enzyme complexed with and without the aminopropyl group donor S-adenosylmethionine. Despite sequence and structural similarity with spermidine synthases from other organisms, a novel C-terminal β-sheet and differences in the catalytic site were observed. The C-terminal module interacts with the gatekeeping loop and fixes the open conformation of the loop to recognize larger polyamine substrates such as agmatine and spermidine. Additional computational docking studies suggest that the structural differences of the catalytic site also contribute to recognition of the aminopropyl/aminobutyl or guanidium moiety of the substrates of TAAPT. These results explain in part the extraordinarily diverse polyamine spectrum found in T. thermophilus.
- Ohnuma, Mio,Ganbe, Tadashi,Terui, Yusuke,Niitsu, Masaru,Sato, Takao,Tanaka, Nobuo,Tamakoshi, Masatada,Samejima, Keijiro,Kumasaka, Takashi,Oshima, Tairo
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experimental part
p. 971 - 986
(2012/05/20)
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- Metabolism of N-alkylated spermine analogues by polyamine and spermine oxidases
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N-alkylated polyamine analogues have potential as anticancer and antiparasitic drugs. However, their metabolism in the host has remained incompletely defined thus potentially limiting their utility. Here, we have studied the degradation of three different spermine analogues N,N′-bis-(3-ethylaminopropyl)butane-1,4-diamine (DESPM), N-(3-benzyl-aminopropyl)-N′-(3-ethylamino-propyl)butane-1,4-diamine (BnEtSPM) and N,N′-bis-(3-benzylaminopropyl)butane-1,4-diamine (DBSPM) and related mono-alkylated derivatives as substrates of recombinant human polyamine oxidase (APAO) and spermine oxidase (SMO). APAO and SMO metabolized DESPM to EtSPD [Km(APAO) = 10 μM, kcat(APAO) = 1.1 s -1 and Km(SMO) = 28 μM, kcat(SMO) = 0.8 s-1, respectively], metabolized BnEtSPM to EtSPD [Km(APAO) = 0.9 μM, kcat(APAO) = 1.1 s-1 and Km(SMO) = 51 μM, kcat(SMO) = 0.4 s-1, respectively], and metabolized DBSPM to BnSPD [Km(APAO) = 5.4 μM, k cat(APAO) = 2.0 s-1and Km(SMO) = 33 μM, kcat(SMO) = 0.3 s-1, respectively]. Interestingly, mono-alkylated spermine derivatives were metabolized by APAO and SMO to SPD [EtSPM Km(APAO) =16 μM, kcat(APAO) = 1.5 s -1; Km(SMO) = 25 μM, kcat(SMO) = 8.2 s -1; BnSPM Km(APAO) = 6.0 μM, kcat(APAO) = 2.8 s-1; Km(SMO) =19 μM, kcat(SMO) = 0.8 s-1, respectively]. Surprisingly, EtSPD [Km(APAO) = 37 μM, kcat(APAO) = 0.1 s-1; Km(SMO) =48 μM, kcat(SMO) = 0.05 s-1] and BnSPD [Km(APAO) = 2.5 μM, kcat(APAO) = 3.5 s-1; Km(SMO) =60 μM, kcat(SMO) = 0.54 s-1] were metabolized to SPD by both the oxidases. Furthermore, we studied the degradation of DESPM, BnEtSPM or DBSPM in the DU145 prostate carcinoma cell line. The same major metabolites EtSPD and/or BnSPD were detected both in the culture medium and intracellularly after 48 h of culture. Moreover, EtSPM and BnSPM were detected from cell samples. Present data shows that inducible SMO parallel with APAO could playanimportant roleinpolyamine based drug action, i.e. degradation of parent drug and its metabolites, having significant impact on efficiency of these drugs, and hence for the development of novel N-alkylated polyamine analogues. Springer-Verlag 2009.
- Haekkinen, Merja R.,Hyvoenen, Mervi T.,Auriola, Seppo,Casero Jr., Robert A.,Vepsaelaeinen, Jouko,Khomutov, Alex R.,Alhonen, Leena,Keinaenen, Tuomo A.
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p. 369 - 381
(2010/11/18)
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- Chemoenzymatic syntheses of polyamines and tetraazamacrocycles
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Syntheses of different open chain polyamines starting from enzymatically prepared bis(amidoesters) are described. Some of these polyamines are also used as precursors in the syntheses of tetraazamacrocycles. This methodology can also be applied to the synthesis of chiral compounds.
- Rubio, Mercedes,Astorga, Covadonga,Alfonso, Ignacio,Rebolledo, Francisca,Gotor, Vicente
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p. 2441 - 2452
(2007/10/03)
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- Chemistry of the diazeniumdiolates. 2. Kinetics and mechanism of dissociation to nitric oxide in aqueous solution
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Diazeniumdiolate ions of structure R2N[N(O)NO]- (1) are of pharmacological interest because they spontaneously generate the natural bioregulatory species, nitric oxide (NO), when dissolved in aqueous media. Here we report the kinetic
- Davies,Wink,Saavedra,Keefer
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p. 5473 - 5481
(2007/10/03)
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The reaction of spermine with aromatic aldehyde leads to an equilibrated system between the bis imine form 1′ and the hexahydropyrimidine form 1. In contrary the formaldehyde adduct of spermine exist only on the hexahydropyrimidine form 9. 1-1′ is readily hydrolyzed by HCl with regeneration of the aldehyde and spermine. The NaBH4 reduction of 1-1′ leads to the dibenzyl spermine 8 and the phosphonate adducts 2 or 6 are obtained from 1-1′ and a hydrogen phosphonate. These last two reactions failed with 9. Inversely 9 and 1-1′ reacts equably well with tetramethyl chloro dioxaphospholane with formation of cyclic phosphinamidates 10 and 5. In the second case a kinetic intermediate 3 can be observed by 31P NMR.
- Bailly, Theodorine,Burgada, Ramon
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- Process for the dyeing of leather with anionic dyes and polyaminoamide resin as dyeing auxiliary
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To improve the affinity of anionic dyestuffs in the dyeing of leather materials, polycondensation products consisting of at least one amine of the formula STR1 in which the radicals have the meanings mentioned in the description with one dicarboxylic acid and, if desired, ω-aminocarboxylic acid or its lactam are highly suitable.
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- CHENGES IN POLYAMINES AND RELATED ENZYMES WITH LOSS OF VIABILITY IN RICE SEEDS.
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Putrescine, spermidine and spermine of high vigour, low vigour and non viable (classes 1, 2 and 3 respectively) seeds of Oryza sativa increased with loss of viability.The largest concentration of spermine was found in non-viable embryos.Spermine was absent in the husks of all the three categories of seeds.Arginine decarboxylase was greatest in high vigoured seeds and its activity gradually declined with loss of viability.However, diamine oxidase and polyamine oxidase activities gradually increased with the loss of viability of the seeds while DNA, RNA and protein contents decreased.The total content of polyamines increased on kinetin treatment but declined on ABA treatment.DNA, RNA and protein followed the same trend as polyamines.The polyamine contents increased by ca 3- and 4-fold, respectively, in high vigoured and low vigoured seeds on 1E-4 M kinetin treatment.The activity of ADC followed the same change as that of the polyamines in both cases, but the reverse was observed for the activities of diamine and polyamine oxidases.Key Word Index - Oryza sativa; Gramineae; rice; spermine; spermidine; putrescine; arginine; arginine decarboxylase; polyamine oxidase.
- Mukhopadhyay, A.,Choudhuri, M. M.,Sen, K.,Ghosh, B.
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p. 1547 - 1552
(2007/10/02)
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- Chemistry of Naturally Occuring Polyamines. 1. Total Synthesis of Celacinnine, Celabenzine, and Maytenine
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New methods for the selective functionalization of spermidine and other naturally occurring polyamines have been employed in highly convergent total syntheses of the title compounds.
- McManis, James S.,Ganem, Bruce
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p. 2041 - 2042
(2007/10/02)
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