Putrescine alkaloids

Concerning the nature of the polyamine alkaloids, characteristic differences exist. In the case of putrescine alkaloids the base is always a chain in spermidine and spermine alkaloids the cyclic form is predominant. The 13-membered and 17-membered lactams are the preferred rings in the spermidine and spermine alkaloids, respectively. As shown in Scheme 41... 

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. 

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 pivotal role of hygrine in the biosynthesis of cuscohygrine and of the tropane alkaloids has justified numerous investigations. The following scheme represents the now generally admitted pattern of formation of these bases. Ornithine (119) is first converted to putrescine or V-methylputrescine (120)... 

Although no experiment has yet been reported to support the idea, it seems clear that a majority of the pyrrolidine alkaloids arise from the ornithine, pu-trescine, and proline pool. This could be the case for ficine (61) and isoficine (62), vochysine (63), and phyllospadine (64) but also of the Darlingia alkaloids, which share common features with hygrine this assertion probably also holds for the ruspolinone (25) and odorine-roxburghlin (59) families. Peripentadenine, isolated from a plant of the family Elaeocarpaceae, bears resemblance to other alkaloids of the elaeocarpus type such as isoelaeocarpicine (124) (161). It cannot be excluded, however, that spermidine may be a biosynthetic intermediate instead of putrescine. The question of the origin of ant alkaloid substances remains so far without an obvious answer. 

The synthesis of alkaloids from L-ornithine starts with decarboxylation by the Pyridoxal Phosphate (PLP) to putrescine (Figure 33) and putrescine metylation by 5 -Adenosylmethionine (SAMe) to A-methylputrescine. The SAM is a naturally occurring reaction, when the departing groups convert... 

Figure 33. Synthesis of alkaloids from ornithine. Aikaioids are derived via putrescine or glutamic semialdehyde. At least two enzymes, ODL (Ornithine decarboxylase) or PDL (Pyrroline...

The synthesis of tropine from tropinione requires dehydrogenase NADPH+. Similarly, the synthesis of cocaine requires the Mannich reaction, SAM and NADPH+. Putrescine is a biogenic amine. Other biogenic amines also participate in alkaloid synthesis, for example cadaverine in the case of lysine alkaloids. Aniszewski et al. " drew attention to the fact that the various biogenic amines... 

The pyrrolizidine nucleus is characteristic of this group of alkaloids. The a is either L-ornithine or L-arginine, and the /3 is a biogenic amine, the putrescine. Oxidative deamination by enzyme NAD+ converts two molecules of putrescine... 

Pyrrolidine alkaloids have a pyrrolidine (C4N skeleton) nucleus. The structural a of these alkaloids is L-ornithine (in plants) and L-arginine (in animals). The pyrro-line skeleton is synthesized after /3 (putrescine) and

Schiff base reaction forms which is A-methyl-A -pyrrolinium cation. Subsequently, A (hygrine) is formed. Typical pyrroline alkaloids are (-)- and (-1-)- hygrines (Figure 56). 

Hibi et al. " have reported on putrescine A-methyltransferase isolated from the nicotine biosynthetic pathway coded by cDNA. Recent advances in cell and molecular biology of alkaloid biosynthesis have heightened awareness of the genetic importance. 

Brevicolline.—The /3-carboline part of the plant alkaloid brevicolline (114) has been shown to derive from tryptophan (94) and pyruvic acid.37 Putrescine (4) and related compounds provide the pyrrolidine ring.38 A key intermediate in brevicolline biosynthesis is likely to be (113), derived by oxidative decarboxylation of (111), which in turn is formed through the condensation of (94) with pyruvic acid condensation of (113) and (112) (formed from putrescine) would lead to (114). This has been supported by successfully mimicking the biogenetic sequence, starting with the chemical oxidative decarboxylation of (111).39... 

Simple Pyrrolidine Alkaloids.—It is well established that ornithine (1) is a key precursor in the biosynthesis of pyrrolidine alkaloids. Notably, the amino-acid (1) is utilized for the biosynthesis of nicotine (5) via the symmetrical intermediate putrescine (3), whereas the biosynthesis of tropane alkaloids, e.g. scopolamine (6), avoids any symmetrical intermediate1,2 (cf. Vol. 11. p. 1). 

The biosynthetic pathway to both nicotine (5) and the tropane alkaloids includes A-methylputrescine (4) as a probable intermediate. New results6 obtained for nicotine (5) and scopolamine (6) with 1 l-13C,14C wef/zy/awmo-15Nl-A-methyl putrescine 1(4) labels as shown nicely confirm this. The specific incorporation of both stable isotopes was closely similar to that of the 14C label in both alkaloids, indicating intact incorporation of the precursor. The labelling patterns deduced are illustrated ( = 13C, = 15N), and they are in accord with earlier results that were... 

Pyrrolizidine Alkaloids.—Retronecine (23), the most common base portion found in the pyrrolizidine alkaloids, has been shown to derive from two molecules of ornithine (1) via putrescine (3) by the use of 14C-labelled precursors19 (cf. Vol. 10, p. 13). Unequivocal evidence on the manner of incorporation of putrescine comes from experiments in Senecio isatideus with 13C-labelled samples of putrescine.20... 

Figure 9.2. Metabolism of pyrrolizidine alkaloids (PAs) in Senecio vernalis. The substrates for alkaloid biosynthesis, putrescine and spermidine, are derived from primary metabolism. Homospermidine, synthesized by homospermidine synthase (HSS), is the first pathway specific intermediate. It is exclusively incorporated into the necine base moiety of senecionine A-oxide, the backbone structure of all PAs found in this Senecio species. During allocation from the roots as site of synthesis to the shoots, it is chemically modified to provide the species specific PA-pattem.

BOTTCHER, F., OBER, D., HARTMANN, T., Biosynthesis of pyrrolizidine alkaloids Putrescine and spermidine are essentail substrates of enzymatic homospermidine formatioa Can. J. Chem., 1994,72, 80-85. 

Pyrrolidine is the simple five-membered cyclic amine and pyrrolidine alkaloids contain this ring somewhere in their structure. Both nicotine and atropine contain a pyrrolidine ring as do hygrine and tropinone. All are made in nature from ornithine. Ornithine is an amino acid not usually found in proteins but most organisms use it, often in the excretion of toxic substances. If birds are fed benzoic acid (PI1CO2H) they excrete dibenzoyl ornithine. When dead animals decay, the decarboxylation of ornithine leads to putrescine which, as its name suggest, smells revolting. It is the smell of death . 

PUTRESCINE, SPERMIDINE, SPERMINE, AND RELATED POLYAMINE ALKALOIDS... 

Until now only putrescine and 2-hydroxyputrescine have been found as basic skeletons of diaminoalkane alkaloids of this type. ... 

A number of putrescine derivatives have been detected in nature for which one or two cinnamic acid analogs with amide linkages are known 4-coumaroylputrescine (2), di-4-coumaroylputrescine (3), feruloylpu-trescine (4) (subaphylline), diferuloylputrescine (5), caffeoylputrescine (6) (paucine), dicaffeoylputrescine (7), sinapoylputrescine (8), and disinapoyl-putrescine (9). Paucine, one of the first diaminoalkane alkaloids known since 1894 as a component of the seed of Pentaclethra macrophylla, was hydrolyzed (40% KOH - H20) to give putrescine and caffeic acid. Structure 6 was deduced (37) from this data together with spectroscopic data, especially mass spectra. Another derivative of putrescine, subaphylline (4), first isolated from Salsola subaphylla, was shown to be the monoferuloyl derivative of putrescine by hydrolysis (30% K0H-H20) (38). The structure elucidation of the other derivatives of putrescine (2, 3, 5, 7-9) mentioned before was undertaken in a manner similar to that of 4 and 6. Several compounds were synthesized and compared to the natural products and are summarized in Table II of Section V. 

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