Apparicine

File:Formación de uleina y aparicina.png of apparicine and uleine have a similar pathway.|left|300x300px]]The alkaloid has been isolated from seven species of Aspidosperma.{{sfn|Monteiro|1966|p=39}} It is the principal alkaloid found in the callus of Tabernaemontana elegans, and has also been identified in other Tabernaemontana species, including T. africana, T. divaricata, T. orientalis, and T. pachysiphon.{{sfn|Verpoorte|van der Heijden|Schripsema|Sierra|1989|p=139}}{{sfn|Elia|2008|p=593}} In studies of T. pachysiphon, it was found that alkaloid content including that of apparicine was greatest in young leaves and leaves receiving greater shade, and varied with leaf age, plant age, and provenance.{{sfn|Elia|2008|p=596}}

Research on Aspidosperma pyricollum has led to the discovery that apparicine is biosynthesised from tryptophan by "loss of C-2 and retention of C-3".{{sfn|Shamma|1970|p=324}} The biosynthesis of apparicine requires alteration of the usual tryptamine side chain with loss of C-1.{{sfn|Herbert|1983|p=13}}

Its structure was established through the methods of chemical decomposition, and the nascent field of nuclear magnetic resonance (NMR) decoupling using the ¹H isotope of hydrogen.{{sfn|Joule|Allen|Bishop|Harris|1980|p=230}} Ultraviolet–visible spectroscopy showed that apparicine has a similar UV absorption to uleine,{{sfn|Joule|1983|p=287}} and their chromophores were found to be identical.{{sfn|Joule|Allen|Bishop|Harris|1980|p=230}}

NMR decoupling experiments revealed that apparicine lacks an N-methyl signal and has one methylenic carbon atom between the nitrogen atom and the indole rings, allowing researchers to distinguish it from uleine.{{sfn|Joule|1983|p=287}} This was a notable early use of NMR decoupling to determine a chemical structure.{{sfn|Joule|1983|p=287}} Its carbon skeleton was found to be related but different from that of uleine, and the structures of vallesamine and O-acetyl-vallesamine to be related to apparicine.{{sfn|Biemann|1966|p=40}}

Dehydrogenation of apparicine followed by oxidation with permanganate allowed location of the two piperidine ring carbon substituents.{{sfn|Joule|1983|p=288}}

Apparicine may have several potential applications. In cell cultures, it has shown cytotoxicity against the experimental lymphocytic leukemia P388 cell line.{{sfn|Schmelzer|2008|p=592}} It exhibits strong activity against poliovirus type 3 (PV3),{{sfn|Schmelzer|2008|p=592}} and has moderate to strong activity against some human pathogens.{{sfn|Mairura|Schmelzer|2008|p=590}} It is also active at opioid receptors{{sfn|Schmelzer|2008|p=592}} and has micromolar affinity for adenosine receptors.{{sfn|Ingkaninan|Ijzerman|Taesotikul|Verpoorte|1999|p=1441}} Apparicine has local analgesic properties.{{sfn|Mairura|Schmelzer|2008|p=590}} It inhibited xanthine oxidase as potently as allopurinol (IC₅₀ = 0.65 μM).{{cite journal |vauthors=Shi BB, Chen J, Bao MF, Zeng Y, Cai XH |title=Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activity |journal=Phytochemistry |volume=166 |issue= |pages=112060 |date=October 2019 |pmid=31302343 |doi=10.1016/j.phytochem.2019.112060 |s2cid=196613130 |url= |issn=}}

• Catharanthine
• Pericine
• Tabernaemontanine

{{reflist|30em}}

{{refbegin|30em}}

• {{cite book|last=Biemann|first=Klaus|date=1966|chapter=Mass spectrometry of selected natural products|editor-last=Zechmeister|editor-first=L.|title=Fortschritte der Chemie organischer Naturstoffe |volume=24|publisher=Springer-Verlag|pages=2–98|doi=10.1007/978-3-7091-8143-0_1|isbn=978-3-7091-8145-4|pmid=5958065}}
• {{cite encyclopedia|last=Elia|first=J.|editor1-last=Schmelzer|editor1-first=G. H.|editor2-last=Gurib-Fakim|editor2-first=A.|encyclopedia=Medicinal Plants 1|title=Tabernaemontana pachysiphon Stapf|date=2008|publisher=PROTA Foundation; Backhuys Publishers; CTA|series=Plant Resources of Tropical Africa|volume=11|isbn=978-90-5782-204-9|pages=593–596}}
• {{cite book|last1=Gilbert|first1=B.|date=1968|chapter=The alkaloids of Aspidosperma, Ochrosia, Pleiocarpa, Melodinus, and related genera|editor-last=Manske|editor-first=R. H. F.|title=The Alkaloids: Chemistry and Physiology|volume=11|publisher=Academic Press|pages=205–306|doi=10.1016/S1876-0813(08)60121-9|isbn=978-0-12-469511-5}}
• {{cite book|last=Herbert|first=Richard B.|date=1983|chapter=Structural and biosynthetic relationships|editor-last=Saxton|editor-first=J. Edwin|title=Indoles: Part Four: The Monoterpenoid Indole Alkaloids|series=The Chemistry of Heterocyclic Compounds|volume=25|publisher=John Wiley & Sons|pages=1–46|doi=10.1002/9780470186954.ch1|isbn=0-471-89748-5|url=https://archive.org/details/indolesmonoterpe0000unse/page/1}}
• {{cite journal|last1=Ingkaninan|first1=K.|last2=Ijzerman|first2=A. P.|last3=Taesotikul|first3=T.|last4=Verpoorte|first4=R.|date=1999|title=Isolation of opioid-active compounds from Tabernaemontana pachysiphon leaves|journal=Journal of Pharmacy and Pharmacology|volume=51|issue=12|pages=1441–1446|doi=10.1211/0022357991777092|pmid=10678501|s2cid=45544097|doi-access=free}}
• {{cite book|last=Joule|first=John A.|date=1983|chapter=The uleine–ellipticine–vallesamine group|editor-last=Saxton|editor-first=J. Edwin|title=Indoles: Part Four: The Monoterpenoid Indole Alkaloids|series=The Chemistry of Heterocyclic Compounds|volume=25|publisher=John Wiley & Sons|pages=[https://archive.org/details/indolesmonoterpe0000unse/page/265 265–292]|doi=10.1002/9780470186954.ch1|isbn=0-471-89748-5|chapter-url=https://archive.org/details/indolesmonoterpe0000unse/page/265}}
• {{cite book|last1=Joule|first1=J. A.|last2=Allen|first2=M. S.|last3=Bishop|first3=D. I.|last4=Harris|first4=M.|last5=Hignett|first5=G. J.|last6=Scopes|first6=D. I. C.|last7=Wilson|first7=N. D. V.|display-authors=4|date=1980|chapter=Approaches to the synthesis of apparicine|editor1-last=Phillipson|editor1-first=John David|editor2-last=Zenk|editor2-first=M. H.|title=Indole and Biogenetically Related Alkaloids|series=Annual Proceedings of the Phytochemical Society of Europe|volume=17|publisher=Academic Press|pages=229–248|isbn=0-12-554450-2}}
• {{cite journal|last1=Joule|first1=J. A.|last2=Monteiro|first2=H.|last3=Durham|first3=L. J.|last4=Gilbert|first4=B.|last5=Djerassi|first5=Carl|display-authors=4|date=1965|title=Alkaloid studies. Part XLVIII. The structure of apparicine, a novel Aspidosperma alkaloid|journal=Journal of the Chemical Society|issue=4|pages=4773–4780|doi=10.1039/JR9650004773|pmid=5891947}}
• {{cite encyclopedia|last1=Mairura|first=F. S.|last2=Schmelzer|first2=G. H.|editor1-last=Schmelzer|editor1-first=G. H.|editor2-last=Gurib-Fakim|editor2-first=A.|encyclopedia=Medicinal Plants 1|title=Tabernaemontana crassa Benth.|date=2008|publisher=PROTA Foundation; Backhuys Publishers; CTA|series=Plant Resources of Tropical Africa|volume=11|isbn=978-90-5782-204-9|pages=589–592}}
• {{cite book|title=Studies on some indole alkaloids: the structure of vallesiachotamine. apparicine, an indole alkaloid of novel structure. the structure and chemistry of nervobscurine. tubulosine and its chemical correlation with deoxytubulosine, Parts 1–4|last=Monteiro|first=Hugo Jorge|year=1966}}
• {{cite encyclopedia|last=Schmelzer|first=G. H.|editor1-last=Schmelzer|editor1-first=G. H.|editor2-last=Gurib-Fakim|editor2-first=A.|encyclopedia=Medicinal Plants 1|title=Tabernaemontana elegans Stapf|date=2008|publisher=PROTA Foundation; Backhuys Publishers; CTA|series=Plant Resources of Tropical Africa|volume=11|isbn=978-90-5782-204-9|pages=592–593}}
• {{cite book|last=Shamma|first=Maurice|date=1970|chapter=Alkaloids|editor-last=Cain|editor-first=Cornelius K.|display-editors=etal|title=Annual Reports in Medicinal Chemistry, 1969|publisher=Academic Press|pages=323–332|doi=10.1016/S0065-7743(08)60353-X|isbn=978-0-12-040505-3}}
• {{cite book|last1=Verpoorte|first1=R.|last2=van der Heijden|first2=R.|last3=Schripsema|first3=J.|last4=Sierra|first4=M.|last5=Pennings|first5=E. J. M.|last6=van Iren|first6=F.|last7=ten Hoopen|first7=H. J. G.|display-authors=4|date=1989|chapter=Secondary metabolites in cell cultures of Teabernaemontana species|editor-last=Kurz|editor-first=Wolfgang G. W.|title=Primary and Secondary Metabolism of Plant Cell Cultures II|publisher=Springer-Verlag|pages=138–148|doi=10.1007/978-3-642-74551-5_16|isbn=978-3-642-74553-9}}

{{refend}}

• [https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID30415108 (-)-Apparicine] in the United States Environmental Protection Agency's CompTox Database
• [http://kanaya.naist.jp/knapsack_jsp/information.jsp?sname=C_ID&word=C00001689 (-)-Apparicine] at KNApSAck

{{Opioid receptor modulators}}

Category:Indole alkaloids

Category:Vinylidene compounds

Category:Terpenes and terpenoids