Spermine reactions

Figure 31-3. Arginine, ornithine, and proline metabolism. Reactions with solid arrows all occur in mammalian tissues. Putrescine and spermine synthesis occurs in both mammals and bacteria. Arginine phosphate of invertebrate muscle functions as a phosphagen analogous to creatine phosphate of mammalian muscle (see Figure 31-6).

Figure 9 summarizes the electrode responses toward a variety of DNA-binding substrates [14c]. For intercalators (quinacrine, acridine orange, and safranin) and groove binders (spermine and spermidine), a steep rise followed by a saturation of the concentration response curve is commonly observed. If one compares the specific concentration which gives a 50% response in the increment of the cathodic peak current (A/p ) for each substrate, a selectivity order of quinacrine acridine orange > spermine > spermidine > safranin can be estimated. The binding constants measured in aqueous media for the affinity reaction with ds DNA are as follows quinacrine, 1.5 x 10 (38 mM NaCl)... 

Chiral spermine-bridged cyclotriphosphazenes 21 have been synthesized by the reaction of a gi r -disubstituted cyclophosphazene 188 with spermine (Equation 34). The chiral products are also accessible by derivatizing a spermine-bridged cyclophosphazene <2002JCD365>. 

Kamei et al. [45] separated spermine, spermidine, putrescine, and cadav-erine in an ion-pair reversed-phase LC system and detected the hydrogen peroxide formed in the reaction catalyzed by the enzymes putrescine oxidase and polyamine oxidase with POCL. The same analytes were determined in a later study [46], together with the acetyl derivatives. The sensitive determination of uric acid, selectively converted to hydrogen peroxide by uricase, has been investigated by several authors [37, 47],... 

The venoms of many kinds of bees, wasps, and hornets (the genera Vespa, Polistes, Vespula, Ropalidia, etc.) contain biogenic amines such as histamine (136), serotonin (141), and catecholamines in addition to polyamines such as putrescine (111), spermidine (110), and spermine (112) (Table VIII). The biogenic amines in the venoms act as the main pain-producing principles 46). The contents of these amines in the venom may affect the severity of pain production, edematous reaction of the skin, or increase in skin permeability by stings of these insects. Consequently these amines act as toxins for their defense, together with acetylcholine, enzymes, and peptides 47). 

A third biosynthetic pathway to /-alanine 3 by oxidation of spermidine 13 and spermine 1 has been recently elucidated in yeast [17]. This reaction starts by transformation of L-methionine 15 to decarboxyadenosylmethionine (dcAdoMet, 16). The latter alkylates putrescine 12 at one or both nitrogens generating spermidine 13 and spermine 1 which are oxidized to 3-aminopropanal 14 and further to /-alanine (Scheme 1.6.4). 

The transamidation reaction has been successfully applied to the syntheses of a number of natural polyamino alkaloids. These alkaloids contain principally spermidine or spermine as the basic skeleton [37],... 

In addition to spermidine, spermine was isolated among the products of a KOH melt reaction and characterized as its tetraacetyl derivative [compare with (24)]. By an additional degradation of spermine, spermidine is formed. 

To resolve the question of the connection of spermine with the benzofuran system, the compounds 185 (Scheme 33) and 186 (Scheme 34) were prepared and analyzed. In 179 the units are connected by three bonds, two of which are amide bonds. One of the amides is N-monosubstituted and must therefore represent one end of the spermine unit. By treatment of 180 with benzoyl chloride this N-substituted amide is transformed to an N-sub-stituted secondary amid (imide), which under mild hydrolysis conditions [preferred cleavage of the N-23—C-24 bond] followed by esterification yielded 185. Deuteration experiments, transformation reactions with 185, as well as extensive spectroscopic investigations, have shown that in 179 N-23 is connected to C-24 and not to C-19. 

The structure elucidation of the main alkaloid 194 was based primarily on the products of a Hofmann degradation reaction resulting in the base 198 (see Scheme 36). The observation was made that homaline, which contains no formal C=C double bonds apart from the two benzene rings, can be transformed (H2/Pd-C) to an open-chained spermine derivative. This derivative can be converted to 199 by methylation (H2CO/H2/Pd-C). The structure of homaline as 194 follows from these properties. Compound 199 was also obtained by hydrogenation of the Hofmann base 198. A structural alternative to 194 could be excluded on the basis of spectroscopic arguments. Similar investigations led to the formulas 195,196, and 197 for the three minor alkaloids. 

Verbascenine (205) has been isolated from the aerial parts of Verbascum species (140). Its structure elucidation was based on chemical degradation reactions as well as careful analysis of spectral data (140). In addition to spermidine, spermine was isolated from a KOH melt reaction and identified as its tetraacetyl derivative. The two cinnamic acid residues were identified by spectroscopic methods. A C=C double bond was found in only one of these units. The other cinnamic acid residue is part of a / -aminodihydrocin-namide. Therefore, verbascenine must be cyclic. The number of possible structures was reduced to two (205 and 206) on the basis of the formation of certain derivatives and their spectroscopic properties. Structure 205 is preferred for verbascenine because of the mass spectral behavior of its... 

Besides synthesis, Hofmann degradation of 208 has established that spermine is part of the pithecolobines. By this degradation reaction, a number of different alkylamines were formed and identified. The question of whether all pithecolobines contain spermine or whether compounds also exist that contain the l,12-diamino-4,8-diazadodecane (thermospermine) has not yet been answered completely. 

The reaction of N3P3C16 with spermine (2 1) leads to a unique final product which has a two-ring assembly structure in which two SPIRO NjPjCIJHN—(CH —N] moieties are bridged through a (CH2)4 chain in a BINO configuration. We propose to call the new configuration observed here DISPIROBINO. 

MC and DC structures containing two and one PC12 moieties respectively, reaction of these chemicals with spermine in (2 1) conditions may generate the symmetrical isomer DSs of DSa and TetS respectively. 

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