Lupinine epilupinine

Sodium borohydride reduction of 4-substituted isoquinolinium salts led to vinylogous cyanamides, ureas, and urethanes, as well as the corresponding tetrahydroquinolines (640). Hydrogenation of /8-acylpyridinium salts (641) to vinylogous ureas was exploited in syntheses of alkaloids (642), leading, for instance, to lupinine, epilupinine, and corynantheidine (643, 644). Similarly, syntheses of dasycarpidone and epidasycarpidone were achieved (645) through isomerization of an a,/0-unsaturated 2-acylindole and cyclization of the resultant enamine. 

Quinolizidine synthesis via intramolecular immonium ion based Diels-Alder reactions total synthesis of ( )-lupinine, ( )-epilupinine, ( )-criptopleurine and ( )-julandine [97]... 

The most common group of alkaloids possessing a quinolizidine nucleus is that of the lupine alkaloids which can simply be classified as bicyclic (lupinine/epilupinine type), tricyclic (cytisine type) or tetracyclic, (sparteine/lupanine or matrine type). Fig. (23). This grouping is made according to structure complexity and without considering biosynthesis, as the detailed biosynthetic pathways are still not completely understood. 

Reductive formylation of angustifoline (6) leads to N-methylangustifoline in methanol and to an isomer (7) of the latter in aqueous solution. Derivatives of lupinine, epilupinine, and cytisine have been prepared. 

Lupanine Angustifoline Lupinine Epilupinine Anagiryne Sparteine Swainsonine Castanospermine Hordenine Tyramine Mescaline Anhalamine Anhalonine Anhalonidine Salsolinol Curare... 

Another useful route to alkaloids involves the electrochemical oxidation of lactams (145) bearing functionality on nitrogen that can be used to intramolec-ularly capture an intermediate acyl im-minium ion (146). The concept is portrayed in Scheme 33 and is highlighted by the synthesis of alkaloids lupinine (150) and epilupinine (151) shown in Scheme 34 [60]. Thus, the electrooxidation of lactam (147) provided a 71% yield of ether (148). Subsequent treatment with titanium tetrachloride affected cyclization and afforded the [4.4.0] bicyclic adduct (149). Krapcho decarbomethoxylation followed by hydride reduction of both the... 

Lupinus luteus L., Lupinus hispanicus L., Lupinus hirsutus L. They have also been found in Anabasis aphyla. In absolute configuration, lupinine is in its (—)-form, which is non-stable thermally, and is easily epimerized to epilupinine, which is a stable (+)- form of lupinine . The melting point of (—)-lupinine is 70-71 °C, of mixed (+ and —)-lupinine 63-64°C, and of (+)-lupinine (synthetic)... 

C. Lupinine and epilupinine contain esters, which have been found in... 

Lupinine (2) is easily epimerized to epilupinine (33), a compound occurring in nature and also formed by synthesis (82-87). The synthesis of optically active natural lupinine and epilupinine was accomplished in 1967 (S5). Optically active... 

Analogous reactions involving the more reactive iminium ions have also been observed. For example, a lupinine synthesis involved (203) as a reactive intermediate (60JA502). The decarboxylation of. the diacid was relatively nonstereospecific giving, after reduction, a mixture of ( )-lupinine and ( )-epilupinine. 

Lupinine-Cytisine Group.—An X-ray analysis of (-)-lupinine hydrochloride and of (+)-epilupinine shows that bond lengths and angles are similar to those of lupinine (cf. Vol. 10, p. 68).16 Aminobenzoate esters of lupinine were prepared by transesterification reactions.17... 

The lactam 143 was treated with m-chloroperbenzoic acid, followed by treatment with acid anhydride to yield the aldehyde 144. Catalytic hydrogenation of unsaturated aldehyde 144 gave saturated aldehyde 145, and reduction of 145 with lithium aluminum hydride provided racemic lupinine 4 and racemic epilupinine 139. 

The synthesis of alkaloids lupinine (106) and epilupinine (107) (Scheme 10) nicely illustrates the methodology [25]. Thus, electrochemical oxidation of lactam 103 (constant current, 50 mA Pt/Pt, Et4NC104) in methanol at room temperature afforded a 71% yield of ether 104 after the passage of 2.8F/mol. Subsequent treatment with titanium tetrachloride affected cyclization to the [4.4.0] bicyclic adduct 105. Krapcho decarbomethox-ylation followed by hydride reduction of both the amide and ester units of the resulting epimeric esters provided the natural products 106 and 107. 

The tosylate of epilupinine (XIV) is thermally stable, whereas that of lupinine (XVIII) is quarternized, the structure of the resulting salt (XIX)... 

A mixture of lupinine and epilupinine is obtainable by the following series of reactions. The betaine XXVI on cyclic hydrogenation and subsequent decarboxylation with 20 % hydrochloric acid gives a mixture of epimeric lupininic acids (XXIX). The dicarboxylic ester XXVIII is also obtained by the mercuric acetate dehydrogenation of the piperidine derivative XXX and by the alkylation of monomeric piperideine with a y-bromopropylmalonic ester. The last route is presumably a first Mannich condensation followed by an alkylation. Hydrolysis of the malonic esters, decarboxylation (XXIV), esterification, and reduction with lithium aluminum hydride complete the synthesis of a mixture which consists of 80% dZ-epilupinine and 20% dMupinine. Thermal... 

A simple synthesis of the lupininic acids has been reported as follows 43) ethyl a-pyridylacetate and an acrylic ester or acrylic nitrile undergo a simple Michael addition and hydrogenation of the product generates an epimeric mixture (7 3 or 1 4, respectively) of epilupininic and lupininic acids. 

Another synthesis under physiological conditions has been reported (36). The piperidinoquinolizidine (LIII), obtainable from epilupinine via bromolupinine, cyclizes when dehydrogenated with mercuric acetate to a mixture of LIV and LV which on reduction with sodium borohydride gives a separable mixture of sparteine and allomatrine. The epimeric piperidinoquinolizidine obtainable from lupinine gives a mixture of fl -isosparteine (LVIII) and allomatridine (LVI). The dehydrogenation... 

BCnight and co-workers approached the synthesis of the unnatural ( + )-enantiomer of lupinine (ent-344) by first resolving racemic 2-(piperidin-2-yl)-ethanol with (+ )-camphorsulfonic acid (357,358). The (i -( + )-enantiomer 362 was then converted into the substituted acetic ester 363, the enolate of which was stereoselectively allylated to give 364 and 365 in isolated yields of 71% and 12%, respectively (Scheme 45). The major isomer 364 was readily hydroborated and cyclized to the bicyclic ester 366, reduction of which completed the first reported synthesis of (+ )-lupinine (ent-344). The optical rotation was measured as +19.5° (c 1, EtOH), which compared favorably with the rotation of natural (- )-lupinine (-21°) recorded under similar conditions (359). It was also hoped that epimeriza-tion of 366 would give the thermodynamically more stable compound 377 in which the ester group is equatorial, after which reduction would provide access to (- )-epilupinine (ent-331). However, the product obtained after these transformations was optically inactive, which indicated that epimerization was accompanied by racemization, probably through base-induced retro-Michael reaction followed by Michael recyclization. 

B. Bicyclic Alkaloids.—Full details of the syntheses of lupinine and epilupinine, first reportedin 1960, have now been published this paper also includes the synthesis of sparteine. 

The isomerisation of ( —)-lupinine (5) to (+)-epilupinine (6) has long been known to be possible by chemical methods, e.g. by refluxing natural (-)-lupinine in benzene with metallic sodium, but the yields are low and not consistently reproducible. A preferred method, which consistently gives yields of 20— 25 %, involves the photochemical isomerisation of lupinine in the presence of acetophenone as sensitiser. ... 

The aerial parts of Lupinus hispanicus B. and R. (var. bicolor Merino) contain four alkaloids, of which three were identified as (+)-epilupinine, (—)-lupinine, and gramine. The fourth alkaloid (Alkaloid Y), an amorphous but apparently homogeneous base, was obtained in such small amounts that it has not yet proved possible to determine its structure.150... 

The total alkaloid content of the aerial portion was approximately 2% from which the following were isolated (+ )-epilupinine (65%), ( —)-lupinine (10%,), gramine (15%,), and an unidentified base (5%) 151). 

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