8-Oxosparteine

In contrast to aphylline, 17-oxosparteine is known to be synthesized only under energetic conditions ... 

Dioxo-3-isoparteine was isolated from Lupinus sericeus (143). The mass spectrum, with M+ at miz 262 and signals at miz 234 (M" — 28) and 206 (M+ - 56), is characteristic for 10- and 17-oxosparteines and successive splitting of two carbonyl groups. Oxidation of p-isosparteine (14) by potassium ferricyanide resulted in 10-oxosparteine (108) as well as 10,17-dioxo-p-isospar-teine (109) (Scheme 13). This confirmed the alkaloid structure. Although 109 was found as a natural compound it had already been synthesized by Bohlmann et al. (144). The problems of configuration and conformation of sparteine (6), a-isosparteine (7), and (3-isosparteine (14) were discussed (145). 

The crude enzyme preparation was found to catalyse the conversion of cadaverine (16) mainly into 17-oxosparteine (27) in the presence of pyruvic acid. The pyruvic acid served as a receptor for the amino-groups of (16) in a transamination reaction, having manifestly a close relationship to alkaloid formation.11 Diamine oxidase activity might have been expected to account for the... 

Quinolizidine Alkaloids.—Important new information (cf. Vol. 11, p. 4) has been obtained on the biosynthesis of quinolizidine alkaloids such as lupanine (27) in experiments with enzyme preparations from Lupinus polyphyllus cell suspension cultures26 and with chloroplasts.27 These alkaloids are formed from three molecules of lysine by way of cadaverine (25),1,2 and the enzymic evidence26,27 is that conversion of cadaverine into these alkaloids occurs without release of intermediates until 17-oxosparteine (26) is generated the enzyme is a transaminase and not a diamine oxidase. 

The enzyme, i.e. lysine decarboxylase, that is required for the conversion of lysine into cadaverine, and thus the first step of alkaloid biosynthesis, has been isolated from chloroplasts of L. polyphyllus,28 Like the majority of amino-acid decarboxylases, this enzyme is dependent on pyridoxal 5 phosphate. Its activity was found not to be affected by the presence or absence of quinolizidine alkaloids. Control of the enzyme by simple product feedback inhibition therefore seems unlikely. The operational parameters of this enzyme resemble those of the 17-oxosparteine synthase. Co-operation between the two enzymes would explain why cadaverine is almost undetectable in vivo. 

Oxosparteine perchlorate hemihydrate, cf. (9), has been shown by X-ray crystallography to have rings a, b, c, and d in chair, chair, boat, and half-chair conformations, respectively 12 the corresponding rings of 17-oxosparteine, cf. (9), are in chair, chair, sofa, and chair conformations.13... 

Direct conversion of diol 395 to cytisine 31a was accomplished by a one-pot procedure. Oxidative cleavage to give the dicarboxylic acid, followed by treatment with aqueous ammonia and catalytic reduction provided racemic cytisine 31a in good yield <20000L4205>. Photolysis in benzene at 254 nm of the nitrone 396 afforded smooth rearrangement to 17-oxosparteine 195 likely through the intermediacy of an oxaziridine derivative (Scheme 80) <2002OL2577>. 

Oxosparteine Feeding deterrent to polyphagous Syntomis larvae 0.1% 32... 

Alkaloid metabolism in lupine was proved by Wink and Hartmann to be associated with chloroplasts (34). A series of enzymes involved in the biosynthesis of lupine alkaloids were localized in chloroplasts isolated from leaves of Lupinus polyphylls and seedlings of L. albus by differential centrifugation. They proposed a pathway for the biosynthesis of lupanine via conversion of exogenous 17-oxosparteine to lupanine with intact chloroplasts. The biosynthetic pathway of lupinine was also studied by Wink and Hartmann (35). Two enzymes involved in the biosynthesis of alkaloids, namely, lysine decarboxylase and 17-oxosparteine synthetase, were found in the chloroplast stoma. The activities of the two enzymes were as low as one-thousandth that of diaminopimelate decarboxylase, an enzyme involved in the biosynthetic pathway from lysine to diaminopimelate. It was suggested that these differences are not caused by substrate availability (e,g., lysine concentration) as a critical factor in the synthesis of alkaloids. Feedback inhibition would play a major role in the regulation of amino acid biosynthesis but not in the control of alkaloid formation. 

Oxosparteine, in contrast with aphylline and lupanine, suffers hydrolysis only under energetic conditions. Its hydrolysis with concentrated hydrochloric acid was reexamined and the resulting amino acids were characterized as their esters (LXVII, LXVIII, LXIV) and the corresponding alcohols. One more ester (LXX) was obtained by first dehydrogenating with mercuric acetate and then reducing with sodium borohydride (64). 

The leaves and stems of Thermopsis montana Nutt. (T. fabacea Hook.) contain five alkaloids, four of which are also contained in the flowers and fruits. Three other alkaloids are also present in trace amounts in all parts of the plant. The five alkaloids isolated and characterised are cytisine and iV-methylcytisine (previously isolated ), hydroxylupanine, anagyrine, and thermopsine apparently iV-methylcytisine is not present in the flowers and fruits. Two of the minor alkaloids were tentatively identified as lupanine and 17-oxosparteine. 

We propose the biosynthetic pathway of the carbon framework of matrine as shown in Fig. 4. This scheme also indicates the pathway for the formation of sparteine and lupanine. The former part of this scheme was proposed by Wink et al. [63], with minor modification by Leete [64], from the in vitro experiments using isolated chloroplasts of leaves of Lupinus. They postulated the presence of 17-oxosparteine as the first key intermediate for the formation of lupanine and sparteine [63]. However, this hypothesis involving 17-oxosparteine synthase was not confirmed by the tracer experiments using and independently conducted by the groups of Spenser [65, 66] and Robins [67]. They, in turn, hypothesized the pathway involving the diiminium cation (73) as the tetracyclic intermediate [68, 69]. The postulation of the presence of this reactive intermediate is consistent with the results of isotope incorporation into lupanine and sparteine. The biosynthetic scheme of matrine can be also drawn by involving the electronically equivalent diiminium cation (76) preceded by additional 1,3-hydride shift or imine-enamine isomerization (74 75). All these reactions take... 

Lupinus sericeus contains (—)-7-hydroxy-p-isosparteine and 10, 17-dioxo-P-isosparteine, which are also sparteines tetracyclic quinolizidine alkaloids with a quinolizidine nucleus. Moreover, other alkaloids from this group include epiaphylline and aphylline, alkaloids from L. latifolius, and (—)-lindenianine, an alkaloid from Lupinus lindenianus and Lupinus verbasciformis. Nuttalline (4p-hydroxy-2-oxosparteine) is a tetracyclic quinolizidine alkaloid from Lupinus nuttalli An alkaloid, sparteine can be converted to a-isosparteine or p-isosparteine, which occurs particularly in Cytisophyllum sessilifolium In contrast to aphylline, 17-oxosparteine is known to be s5mthesized only under energetic conditions. ... 

More recent enzymatic evidence showed that the three molecules of cadaverine are transformed to the quinolizidine ring via enzyme-bound intermediates without the generation of any free intermediates. The enzyme 17-oxosparteine synthase requires four units of pyruvate as the NH2 acceptors and produces four molecules of alanine (Figure 7.33) [64]. 

The aphid Macrosiphon albifrons is attracted to Lupinus species with a characteristic alkaloid pattern. Individuals that had low alkaloid content were not attacked, nor were plants with different quinolizidine alkaloid composition. This aphid excretes a portion of the alkaloids in the honeydew and retains a portion in its body (Wink and Romer, 1986). Another aphid, Aphis cytisorum, which infests broom plants (Cytisus scoparius), accumulates up to 0.5 mg alkaloid per gram fresh weight. The alkaloids are similar in composition to those of the host plant, 17-oxosparteine (25), sparteine (17), 12,13-dehydrosparteine, and lupanine (21) (Wink et al., 1982). 

Fig. 235. Proposed scheme for the biosynthesis of sparteine 1 17-Oxosparteine synthase...

The main QAs in L. luteus are lupinine and its esters (E/Z isomers of (4 -hydroxy-3 -methoxycinnamoyl) lupinine) and ((4 -hydroxycinnamoyl)lupinine) and sparteine minor amounts of p-isosparteine, tetrahydrorhombifoline, 17-oxosparteine, lupanine, feruloyllupinine are present [8, 11]. 

In L. albus leaves the main QAs are albine, angustifoline, and lupanine other alkaloids usually present are sparteine, 11,12-dehydrosparteine, isoangustifoline, tetrahydrorhombifoline, 17-oxosparteine, a-isolupanine, 5,6-dehydrolupanine, 13-angeloyloxymultiflorine, 13-tigloyloxymultiflorine. 13-Hydroxylupanine that is usually very abundant in seeds, in leaves is almost totally esterified [8]. 

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