Putrescine

These compounds are present in almost all mam malian cells where they are believed to be involved in cell differentiation and proliferation Because each ni trogen of a polyamine is protonated at physiological pH (7 4) putrescine spermidine and spermine exist as cations with a charge of + 2 +3 and + 4 respectively... 

Ornithine-Derived Alkaloids. Ornithine (23) undergoes biological decarboxylation reductively to generate either putrescine [110-60-1] (36), or its biological equivalent, and subsequent oxidation and cyclization gives rise to the pyrroline [6724-81-2], (37), C H N. 

B. Putrescine dihydrochloride. A 2-1. wide-mouthed Erlen-meyer flask containing 200 ml. of concentrated hydrochloric acid and 400 g. of cracked ice is clamped in an ice-salt bath and provided with an efficient stirrer (inefficient stirring may lower the yield). The stirring is started, and 80 g. (0.46 mole) of adipyl hydrazide is added all at once, followed by 500 ml. of ether (Note 5). While the temperature is maintained below 10° (Note 6), a solution of 80 g. (1.15 moles) of sodium nitrite in 150 ml. of water is added over about 30 minutes through a dropping funnel whose stem reaches below the bottom of the ether layer, but not into the path of the stirrer. The operations in the next paragraph should be conducted without delay after the completion of the addition of the nitrite. 

The residue of crystalline putrescine dihydrochloride is rinsed onto a Buchner funnel with the aid of 100-200 ml. of absolute ethanol used in several portions. The last portions of ethanol are used as wash liquid for the crystals. The crystals are finally pressed dry and washed with 25 ml. of ether. The air-dried product weighs 53-55 g. (72-74%) and melts above 275. Analysis for chlorine indicates that the salt is anhydrous. Concentration of the filtrate to a volume of about 25 ml. yields an additional 1-2 g. total yield 73-77%. The entire synthesis may be completed in one day. 

If the urethane is to be hydrolyzed immediately, there is no need to isolate it. Instead, after distillation of most of the ether and alcohol from the flask in which the urethane is formed, 700 ml. of concentrated hydrochloric acid is added, and the mixture is heated under reflux for 4 hours. The solution is then distilled from a steam bath under aspirator vacuum (Note 11), and the putrescine dihydrochloride is isolated as described above. The total yield is 55-57 g. (74-77%). 

Solid putrescine dihydrochloride should not be heated unduly long at 100°, as it may turn pink. 

Putrescine dihydrochloride has been prepared by the Hofmann degradation of adipamide 3.. s by the Curtius degradation of adipyl hydrazide through the urethane by the Curtius degradation of adipyl azide obtained from adipyl chloride and sodium azide by the Schmidt degradation of adipic acid with hydrogen azide by the reduction of succinonitrile, succinaldoxime, or 7-phthalimidobutyronitrile with sodium and from N-ben-zoyl-7-iodobutylamine ... 

The unsaturated diamine, CgHgoNj, from the hydrolysis of sphero-physine, on oxidation with permanganate yields the ketoaldehyde, McgCH. CO. CHO fdioxime, m.p. 95-6°, and osazone, m.p. 113-4°) and putrescine, NH2[CH2]4NH2, which indicates that this unsaturated diamine is Me2CH. CH CH. NH[CH2]4. NH2. 

Polyamine (Section 22.4) A compound that contains many amino groups. The term is usually applied to a group of naturally occurring substances, including spermine, spermidine, and putrescine, that are believed to be involved in cell differentiation and proliferation. 

A -Pyrroline has been prepared in low yield by oxidation of proline with sodium hypochlorite (71), persulfate (102), and periodate (103). A -Pyrroline and A -piperideine are products of enzymic oxidation via deamination of putrescine and cadaverine or ornithine and lysine, respectively (104,105). This process plays an important part in metabolism and in the biosynthesis of various heterocyclic compounds, especially of alkaloids. 

The nature of the basic functions was defined by hydrolysis of M in 2N hydrochloric acid at 100°C. This furnished agmatine (I) which was characterized as its picrate and hydrochloride and also by degradation to putrescine (II). 

Eflornithine (difluoromethylornithine, DFMO) inhibits the ornithine decarboxylase of the polyamine pathway, in both the trypanosome and the mammalian cell, by acting as an irreversible competitor of the natural substrate ornithine. Inhibition of ornithine decarboxylase results in depletion of the polyamines, putrescine, spermidine and spermine, which are essential for cell proliferation. Eflornithine selectively harms the parasite and not the mammalian cells, despite acting as an ornithine decarboxylase inhibitor in both cell types. This selectivity is explained by the lower rate of ornithine decarboxylase production in the parasite, as compared to mammalian cells. Due to the high turnover rate, mammalian cells are capable of quickly replenishing inhibited ornithine decarboxylase by newly... 

Hi) Poly amines. In many respects the role of poly amines in plant functioning is still mysterious after many years work. They are almost certainly involved in the control of growth and development through their interactions with nucleic acids and membranes (Smith, 1985). There is increasing circumstantial evidence for their involvement, especially of putrescine, in plant responses to a wide range of stresses including pH, Mg deficiency, osmotic shock, cold, SO2 pollution, and cadmium and ammonium toxicity (Smith, 1985). It remains to be determined, however, how, and indeed whether, putrescine accumulation in response to these diverse stresses is beneficial. 

Flores, H.E. Galston, A.W. (1982). Polyamine and plant stress activation of putrescine biosynthesis by osmotic shock. Science, 217, 1259-60. 

A series of poly(ester-urethane) urea triblock copolymers have been synthesized and characterized by Wagner et al/ using PCL, polyethylene glycol, and 1,4 diisocyanatobutane with either lysine ethyl ester or putrescine, as the chain extender. These materials have shown the elongation at break from 325% to 560% and tensile strengths from 8 to 20 MPa. Degradation products of this kind of materials did not show any toxicity on cells. 

Arginine is the formamidine donor for creatine synthesis (Figure 31-6) and via ornithine to putrescine, spermine, and spermidine (Figure 31-3) Arginine is also the precursor of the intercellular signaling molecule ni-... 

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 31-4. Conversion of spermidine to spermine. Spermidine formed from putrescine (decarboxylated L-ornithine) by transfer of a propylamine moiety from...

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