Pyrrolizidine alkaloid biosynthesis; incorporation of 2H-labelled putrescines into retrorsine

Abstract

The labelling patterns in retrorsine (1 ) derived biosynthetically from [I ,4-2H4]and [2,3-2H4J -putrescine have been established by 2H n.m.r. spectroscopy; in the former case the formation of (9S)-[9-2H]retrorsine ( 12) is consistent with stereospecific addition of hydrogen to the re-face of an aldehyde precursor (RC2HO).Retronecine (6) is the base portion of many pyrrolizidine including retrorsine (l), which is the major alkaloid present in Senecio isatideus plants. Retronecine is derived biosynthetically from L-ornithine or ~-arginine~ via putrescine (2)."' It has been shown that homospermidine (3), formed from two molecules of putrescine, is a later intermediate in the biosynthetic pathway to retronecine.698 An

Biosynthesis of the lupine alkaloids. II. Sparteine and lupanine

“…Recent investigations (1-5) employing I3c-and l3c,I5Nlabelled substrates have confirmed and extended earlier results obtained with I4c-labelled tracers (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) on the biosynthesis of the tetracyclic bisquinolizidine-type lupine alkaloids (e.g., (-)sparteine (1,2,5,7,9,12) (1), (+)lupanine (3-6,8, 10, 1 1, 13, 16) (2), (+)-13a-hydroxylupanine (4,5,8,13,14) (3), (-)multiflorine (12,15) 3 X = O H these alkaloids originate from three C5 chains derived from lysine (9)(10)(11)(12)(13)15) or, more specifically, from L-lysine (5) (16). Cadaverine (1-9, 1 1, 14, 15) (6), the decarboxylation product of lysine, is also a precursor and is, presumably, an intermediate (17) between lysine and the alkaloids.…”

“…This prediction cannot be conclusively confirmed or controverted on the basis of the spectra that are at hand, because of the difficulties of obtaining accurate and reproducible quantitative values for the signal areas of the different signals in the I3C nmr spectrum of a minute sample of compound containing enrichment at individual carbon atoms. At best, it can be said that the spectra that are available (3,4) suggest the possibility that the C15N2 alkaloids that were generated in some of the experiments with [l-I3C,1-15~]cadaverine contained different levels of isotopic enrichment in the two C5N segments, N-1 ,C-2,-3,-4,-5,-6 and N-16,C-15,-14,-13,-12,-11.…”

“…Cadaverine (1-9, 1 1, 14, 15) (6), the decarboxylation product of lysine, is also a precursor and is, presumably, an intermediate (17) between lysine and the alkaloids. The two nitrogen atoms of the C15N2 skeleton of the alkaloids are also derived from lysine (9,15) or cadaverine (1)(2)(3)(4). Two C-N units, C-2,N-1 and C-15,N-16, of the alkaloids are derived from the NH2CH2-group of cadaverine, whereas the other four C-N bonds of the alkaloids are formed in the course of biosynthesis.…”

Biosynthesis of lupanine: incorporation of [3,3-2H2]cadaverine

“…Furthermore, the mode of incorporation of intramolecularly doubly labelled [l-13C,1-15~]cadaverine (8)(9)(10)(11) shows that each of the two nitrogen atoms enters the alkaloids as part of an intact cadaverine-derived C-N fragment, (N-1,C-2 and N-16,C-15, respectively).…”

Quinolizidine Alkaloids: Biochemistry, Metabolism, and Function in Plants and Cell Suspension Cultures

“…The most likely explanation is that an intermediate common to both sparteine and lupanine exists, which could be a dehydrosparteine (36,38). For lupinine biosynthesis see (30,31,34,94,95,99). For the biosynthesis of the cytisine-type alkaloids it has been postulated that lupanine is converted into 5,6-dehydrolupanine which is further oxidized to anagyrine, rhombifoline, cytisine and N-methylcytisine (37).…”