Lupanine

Structural formula
Structure of (+) - lupanine
General
Surname	Lupanine
other names	rel - (7 R , 7a S , 14 R , 14a R ) -dodecahydro-7,14-methano-2 H , 11 H -dipyrido [1,2- a : 1 ', 2'- e ] [1.5 ] diazocin-11-one ( IUPAC ) 2-oxosparteine Spartein-2-on Hydrorhombinin (for L isomer)
Molecular formula	C 15 H 24 N 2 O
Brief description	White, crystalline solid
External identifiers / databases
CAS number 550-90-3 [(+) form] 486-88-4 [(-) - form] 4356-43-8 [racemate] PubChem 91471 ChemSpider 82596 Wikidata Q27103558
properties
Molar mass	248.37 g mol −1
Physical state	firmly
Melting point	40 ° C [(+) - isomer] 98-99 ° C [racemate]
boiling point	185-186 ° C [(+) - isomer] 186–188 ° C [(-) - isomer]
safety instructions
GHS hazard labeling no classification available
Toxicological data	177 mg kg −1 ( LD 50 ,  rat ,  ip ) 1644 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lupanine (also: 2-Oxospartein ) is a tetracyclic, organic compound from the group of quinolizidine - alkaloids .

Historical

The first description of lupanine was after extraction from the seeds of the blue lupine

The name of the compound is derived from its occurrence in the genus Lupinus . When Max Hagen described the substance for the first time in 1885, he named the substance he had extracted lupanine , so that it could be distinguished from the already known substances lupinine and lupinidine . The extraction was carried out using hydrochloric acid alcohol from the seeds of the blue lupins and subsequent processing using potassium hydroxide solution and petroleum ether , whereby the compound was obtained as a light yellow honey-like syrup with a bitter taste.

The compound was first synthesized in 1956. The first enantioselective total synthesis of (+) - and (-) - lupanine took place in 2018 starting from 2,4,6,8 ‐ tetraoxobispidine , which was prepared starting from dimethylmalonate .

Occurrence

The compound occurs naturally in Fabaceae genera such as Lupinus , Genista and Cytisus , the compound often represents the main alkaloid in plants. Furthermore, the substance occurs in some species from the Leontice genus . In general, the compound is accompanied by a variety of minor alkaloids such as sparteine , baptifoline and anagyrin . The white lupine contains the lupanine racemically, while the blue lupine contains predominantly the (+) - enantiomer. The proportion of lupanine in lupine seeds is usually between 50 and 70% of the alkaloids, with the exception of yellow lupine .

biosynthesis

The biosynthesis of lupanine is prepared starting from lysine by means of the lysine decarboxylase to cadaverine . With conversion of pyruvate to alanine , three equivalents of cadaverine are converted to lupanine via an unknown intermediate stage. The occurrence of lupanine instead of sparteine and the occurrence of hydroxylupanine instead of lupanine is presumably controlled by a dominant gene.

Extraction and presentation

The substance is usually in a Soxhlet - extraction from lupine seeds using organic solvents such as n-hexane or petroleum ether recovered. The (±) -lupanine obtained in this way can be separated into the enantiomers by means of racemate resolution ; the recrystallization used for this can be carried out with enantiomerically pure 2,3-dibenzoyltartaric acid.

Alternatively, the substance can be prepared according to the synthetic routes mentioned above. For the enantioselective synthesis of (-) - lupanine, 2,4,6,8 ‐ tetraoxobispidine is reacted with ( 1S ) - 1-phenylethanol in a Mitsunobu reaction , followed by a two-stage diastereoselective reduction . The chiral auxiliary is removed in a Birch reduction and the bicyclic intermediate is converted into a new tricyclic intermediate in a multistage α, N - annulation . This is reduced with sodium borohydride and allylated in a Hosomi-Sakurai reaction , the Boc protective group being removed. After renewed N-allylation, a ring-closing metathesis catalyzed by the Grubbs II catalyst takes place, whereby the target compound (-) - lupanine is obtained after hydrogenation .

properties

Pharmacogolically, anti-arrhythmic, hypotensive and hypoglycaemic effects have been described. The specific angle of rotation in an almost 3% acetone solution is [α] _D  = ± 61 ° or [α] _D ²⁰  = ± 81.2 ° for a 1  M ethanol solution . The (+) - 2,3-dibenzoyl- D -tartate of (-) - lupanine crystallizes in the tetragonal space group P 4 ₃ (space group no. 78) with the lattice constants a = 10.906 Å, c = 27.233 Å and Z = 4th

Individual evidence

1. ↑ ^{a b c d} Anna K. Przybył, Maciej Kubicki: Simple and highly efficient preparation and characterization of ( -) - lupanine and (+) - sparteine . In: Tetrahedron . tape 67 , no. 40 , August 2011, p. 7787-7793 , doi : 10.1016 / j.tet.2011.07.080 .
2. ↑ ^{a b c d e f g} Entry on lupanine. In: Römpp Online . Georg Thieme Verlag, accessed on April 3, 2019.
3. ↑ ^{a b} George Roger Clemo, Richard Raper, Charles Robert Wood Sydney Tennis: The lupine alkaloid . Part III. In: Journal of the Chemical Society . tape 0 , 1931, p. 429-437 , doi : 10.1039 / JR9310000429 .
4. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
5. ↑ ^{a b} Dieter Heß : Biochemical Genetics . An introduction with special consideration of higher plants. Springer Verlag, 2013, ISBN 978-3-642-85766-9 , chap. 6 , p. 106-109 ( limited preview in Google Book Search [accessed April 4, 2019]).
6. ↑ Max Hagen: About the lupanine, an alaloid from the seeds of the blue lupine, Lupinus angustifolius . In: Justus Liebig's Annals of Chemistry . tape 230 , no. 3 , p. 367-384 , doi : 10.1002 / jlac.18852300308 .
7. ↑ GR Clemo, R. Raper, JC Seaton: The lupine alkaloids . Part XVI. The synthesis of externally compensated lupanine. In: Journal of the Chemical Society . tape 0 , 1956, p. 3390-3394 , doi : 10.1039 / JR9560003390 .
8. ↑ ^{a b} Dagmar Scharnagel, Jessica Goller, Nicklas Deibl, Wolfgang Milius, Matthias Breuning: The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids: A Modular “Inside-Out” Approach . In: Angewandte Chemie International Edition . tape 57 , no. January 9 , 2018, p. 2432–2435 , doi : 10.1002 / anie.201712852 ( Open Access ).
9. ↑ Michael Wink: Methods for the detection of lupine alkaloids . ( uni-heidelberg.de [PDF; 958 kB ; accessed on April 4, 2019]).
10. ↑ Gerhard Richter : Metabolic physiology of plants . Physiology and biochemistry of primary and secondary metabolism. Georg Thieme Verlag , 1998, ISBN 978-3-13-442006-7 , chap. 12 , p. 517-518 ( limited preview in Google Book Search [accessed April 4, 2019]).