Originally proposed biosynthesis pathway of sparteine
Sparteine is a lupin alkaloid containing a tetracyclic bis-quinolizidine ring system derived from three C5 chains of lysine, or more specifically, L-lysine.[1] The first intermediate in the biosynthesis is cadaverine, the decarboxylation product of lysine catalyzed by the enzyme lysine decarboxylase (LDC).[2] Three units of cadaverine are used to form the quinolizidine skeleton. The mechanism of formation has been studied enzymatically, as well as with tracer experiments, but the exact route of synthesis still remains unclear.
Tracer studies using 13C-15N-doubly labeled cadaverine have shown three units of cadaverine are incorporated into sparteine and two of the C-N bonds from two of the cadaverine units remain intact.[3] The observations have also been confirmed using 2H NMR labeling experiments.[4]
Enzymatic evidence then showed that the three molecules of cadaverine are transformed to the quinolizidine ring via enzyme bound intermediates, without the generation of any free intermediates. Originally, it was thought that conversion of cadaverine to the corresponding aldehyde, 5-aminopentanal, was catalyzed by the enzyme diamine oxidase.[5] The aldehyde then spontaneously converts to the corresponding Schiff base, Δ1-piperideine. Coupling of two molecules occurs between the two tautomers of Δ1-piperideine in an aldol-type reaction. The imine is then hydrolyzed to the corresponding aldehyde/amine. The primary amine is then oxidized to an aldehyde followed by formation of the imine to yield the quinolizidine ring.[5]
Via 17-oxosparteine synthaseedit
More recent enzymatic evidence has indicated the presence of 17-oxosparteine synthase (OS), a transaminase enzyme.[6][7][8][9][10][11] The deaminated cadaverine is not released from the enzyme, thus is can be assumed that the enzyme catalyzes the formation of the quinolizidine skeleton in a channeled fashion .[9][10][11] 7-oxosparteine requires four units of pyruvate as the NH2 acceptors and produces four molecules of alanine. Both lysine decarboxylase and the quinolizidine skeleton-forming enzyme are localized in chloroplasts.[12]
Biosynthesis of sparteine by 17-oxosparteine synthase
^Golebiewski WM, Spenser ID (1988). "Biosynthesis of the lupine alkaloids. II. Sparteine and lupanine". Canadian Journal of Chemistry. 66 (7): 1734–1748. doi:10.1139/v88-280.
^Rana J, Robins DJ (1983). "Quinolizidine alkaloid biosynthesis: incorporation of [1-amino-15 N, 1-13 C] cadaverine into sparteine". Journal of the Chemical Society, Chemical Communications (22): 1335–6. doi:10.1039/c39830001335.
^Fraser AM, Robins DJ (1984). J. Chem. Soc., Chem. Commun. 22: 1147–9. {{cite journal}}: Missing or empty |title= (help)
^ abAniszewski T (2007). Alkaloids - Secrets of Life, 1st Ed. Elsevier. pp. 98–101. ISBN9780444527363.
^Wink M, Hartmann T (1984). Enzymology of Quinolizidine Alkaloid Biosynthesis; Natural Products Chemistry: Zalewski and Skolik (Eds.). pp. 511–520.
^Wink M (December 1987). "Quinolizidine alkaloids: biochemistry, metabolism, and function in plants and cell suspension cultures". Planta Medica. 53 (6): 509–14. doi:10.1055/s-2006-962797. PMID 17269092.
^Wink M, Hartmann T (May 1979). "Cadaverine--pyruvate transamination: the principal step of enzymatic quinolizidine alkaloid biosynthesis in Lupinus polyphyllus cell suspension cultures". FEBS Letters. 101 (2): 343–6. doi:10.1016/0014-5793(79)81040-6. PMID 446758.
^ abPerrey R, Wink M (1988). "On the Role of Δ1-Piperideine and Tripiperideine in the Biosynthesis of Quinolizidine Alkaloids". Z. Naturforsch. 43 (5–6): 363–369. doi:10.1515/znc-1988-5-607. S2CID 43219650.
^ abRoberts M, Wink M, eds. (1998). Alkaloids: Biochemistry, Ecology, and Medicinal Applications. Plenum Press. pp. 112–114.
^Wink M, Hartmann T (1980). "Enzymatic Synthesis of Quinolizidine Alkaloids in Lupin Chloroplasts". Z. Naturforsch. 35 (1–2): 93–97. doi:10.1515/znc-1980-1-218. S2CID 43624858.
sparteine, class, antiarrhythmic, agent, sodium, channel, blocker, alkaloid, extracted, from, scotch, broom, predominant, alkaloid, lupinus, mutabilis, thought, chelate, bivalent, metals, calcium, magnesium, approved, human, antiarrhythmic, agent, included, va. Sparteine is a class 1a antiarrhythmic agent a sodium channel blocker It is an alkaloid and can be extracted from scotch broom It is the predominant alkaloid in Lupinus mutabilis and is thought to chelate the bivalent metals calcium and magnesium It is not FDA approved for human use as an antiarrhythmic agent and it is not included in the Vaughan Williams classification of antiarrhythmic drugs SparteineClinical dataOther names 6R 8S 10R 12S 7 15 diazatetracyclo 7 7 1 02 7 010 15 heptadecaneAHFS Drugs comInternational Drug NamesATC codeC01BA04 WHO IdentifiersIUPAC name 7a 9a sparteineCAS Number90 39 1 YPubChem CID644020DrugBankDB06727 YChemSpider559096 YUNII298897D62SKEGGD01041 YChEBICHEBI 28827 YChEMBLChEMBL44625 NCompTox Dashboard EPA DTXSID4023591ECHA InfoCard100 001 808Chemical and physical dataFormulaC 15H 26N 2Molar mass234 387 g mol 13D model JSmol Interactive imageDensity1 02 g cm3Melting point30 C 86 F Boiling point325 C 617 F Solubility in water3 04 mg mL 20 C SMILES C1CCN2C C H 3C C H C H 2C1 CN4 C H 3CCCC4InChI InChI 1S C15H26N2 c1 3 7 16 11 13 9 12 14 16 5 1 10 17 8 4 2 6 15 13 17 h12 15H 1 11H2 t12 13 14 15 m0 s1 YKey SLRCCWJSBJZJBV ZQDZILKHSA N Y N Y what is this verify It is also used as a chiral ligand in organic chemistry especially in syntheses involving organolithium reagents Contents 1 Biosynthesis 1 1 Via 17 oxosparteine synthase 2 See also 3 References 4 External linksBiosynthesis edit nbsp Originally proposed biosynthesis pathway of sparteineSparteine is a lupin alkaloid containing a tetracyclic bis quinolizidine ring system derived from three C5 chains of lysine or more specifically L lysine 1 The first intermediate in the biosynthesis is cadaverine the decarboxylation product of lysine catalyzed by the enzyme lysine decarboxylase LDC 2 Three units of cadaverine are used to form the quinolizidine skeleton The mechanism of formation has been studied enzymatically as well as with tracer experiments but the exact route of synthesis still remains unclear Tracer studies using 13C 15N doubly labeled cadaverine have shown three units of cadaverine are incorporated into sparteine and two of the C N bonds from two of the cadaverine units remain intact 3 The observations have also been confirmed using 2H NMR labeling experiments 4 Enzymatic evidence then showed that the three molecules of cadaverine are transformed to the quinolizidine ring via enzyme bound intermediates without the generation of any free intermediates Originally it was thought that conversion of cadaverine to the corresponding aldehyde 5 aminopentanal was catalyzed by the enzyme diamine oxidase 5 The aldehyde then spontaneously converts to the corresponding Schiff base D1 piperideine Coupling of two molecules occurs between the two tautomers of D1 piperideine in an aldol type reaction The imine is then hydrolyzed to the corresponding aldehyde amine The primary amine is then oxidized to an aldehyde followed by formation of the imine to yield the quinolizidine ring 5 Via 17 oxosparteine synthase edit More recent enzymatic evidence has indicated the presence of 17 oxosparteine synthase OS a transaminase enzyme 6 7 8 9 10 11 The deaminated cadaverine is not released from the enzyme thus is can be assumed that the enzyme catalyzes the formation of the quinolizidine skeleton in a channeled fashion 9 10 11 7 oxosparteine requires four units of pyruvate as the NH2 acceptors and produces four molecules of alanine Both lysine decarboxylase and the quinolizidine skeleton forming enzyme are localized in chloroplasts 12 Biosynthesis of sparteine by 17 oxosparteine synthase nbsp Proposed ring cyclization steps nbsp Overall schematicSee also editLupinus Lupin poisoningReferences edit Dewick PM 2009 Medicinal Natural Products 3rd Ed Wiley p 311 Golebiewski WM Spenser ID 1988 Biosynthesis of the lupine alkaloids II Sparteine and lupanine Canadian Journal of Chemistry 66 7 1734 1748 doi 10 1139 v88 280 Rana J Robins DJ 1983 Quinolizidine alkaloid biosynthesis incorporation of 1 amino 15 N 1 13 C cadaverine into sparteine Journal of the Chemical Society Chemical Communications 22 1335 6 doi 10 1039 c39830001335 Fraser AM Robins DJ 1984 J Chem Soc Chem Commun 22 1147 9 a href Template Cite journal html title Template Cite journal cite journal a Missing or empty title help a b Aniszewski T 2007 Alkaloids Secrets of Life 1st Ed Elsevier pp 98 101 ISBN 9780444527363 Wink M Hartmann T 1984 Enzymology of Quinolizidine Alkaloid Biosynthesis Natural Products Chemistry Zalewski and Skolik Eds pp 511 520 Wink M December 1987 Quinolizidine alkaloids biochemistry metabolism and function in plants and cell suspension cultures Planta Medica 53 6 509 14 doi 10 1055 s 2006 962797 PMID 17269092 Wink M Hartmann T May 1979 Cadaverine pyruvate transamination the principal step of enzymatic quinolizidine alkaloid biosynthesis in Lupinus polyphyllus cell suspension cultures FEBS Letters 101 2 343 6 doi 10 1016 0014 5793 79 81040 6 PMID 446758 a b Perrey R Wink M 1988 On the Role of D1 Piperideine and Tripiperideine in the Biosynthesis of Quinolizidine Alkaloids Z Naturforsch 43 5 6 363 369 doi 10 1515 znc 1988 5 607 S2CID 43219650 a b Atta ur Rahman Ed 1995 Natural Products Chemistry Vol 15 Elsevier p 537 ISBN 978 0 444 42691 8 a b Roberts M Wink M eds 1998 Alkaloids Biochemistry Ecology and Medicinal Applications Plenum Press pp 112 114 Wink M Hartmann T 1980 Enzymatic Synthesis of Quinolizidine Alkaloids in Lupin Chloroplasts Z Naturforsch 35 1 2 93 97 doi 10 1515 znc 1980 1 218 S2CID 43624858 External links edit nbsp Wikisource has the text of the 1905 New International Encyclopedia article Sparteine nbsp Media related to Sparteine at Wikimedia Commons Retrieved from https en wikipedia org w index php title Sparteine amp oldid 1172444037, wikipedia, wiki, book, books, library,
