Canadine

Last updated
Canadine
Canadine structure.svg
(S)-(-)-canadine
Names
IUPAC name
9,10-Dimethoxy-2′H-[1,3]dioxolo[4′,5′:2,3]berbine
Systematic IUPAC name
(13aS)-9,10-Dimethoxy-5,8,13,13a-tetrahydro-2H,6H-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinoline
Other names
(S)-Tetrahydroberberine; Xanthopuccine
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.023.468 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C20H21NO4/c1-22-17-4-3-12-7-16-14-9-19-18(24-11-25-19)8-13(14)5-6-21(16)10-15(12)20(17)23-2/h3-4,8-9,16H,5-7,10-11H2,1-2H3/t16-/m0/s1
    Key: VZTUIEROBZXUFA-INIZCTEOSA-N
  • O1c2c(OC1)cc3c(c2)CCN5[C@H]3Cc4ccc(OC)c(OC)c4C5
Properties
C20H21NO4
Molar mass 339.391 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Canadine, also known as (S)-tetrahydroberberine and xanthopuccine, is a benzylisoquinoline alkaloid (BIA), of the protoberberine structural subgroup, and is present in many plants from the family Papaveraceae, such as Corydalis yanhusuo and C. turtschaninovii .

Contents

Biosynthesis

Metabolically, (S)-canadine is derived from (S)-reticuline, a pivotal intermediate in the biosynthesis of numerous BIA structural subgroups, through three enzymatic steps: 1) berberine bridge enzyme to (S)-scoulerine; 2) (S)-scoulerine 9-O-methyltransferase to (S)-tetrahydrocolumbamine; and 3) (S)-canadine synthase/CYP719A21 to (S)-canadine. [1]

(S)-Canadine is the immediate metabolic precursor of berberine, which is produced through the action of the enzyme tetrahydroberberine oxidase. [1]

Canadine structure.svg
(S)-canadine
+ H+
 
 
2 O2
2 H2O2
Canadine
2 O2
2 H2O2
 
Berberin.svg
berberine

It is also an intermediate in the biosynthesis of noscapine, which is likewise a benzylisoquinoline alkaloid, but of the phthalideisoquinoline structural subgroup. [2] [3]

(S)-Canadine, berberine, palmatine, and hydrastine are the major alkaloids present in goldenseal. [4] In Corydalis cava, the enzyme berberine reductase converts berberine back to canadine but as the (R) enantiomer of the product. [5]

Berberin.svg
berberine
+ 2 NADPH
 
 
2 H+
 
Canadine
2 H+
 
 
(+)-canadine.svg
(R)-canadine
+ 2 NADP+
 

This type of inversion of stereochemistry allows both enantiomers of some alkaloids to be present in this species. [6]

Effects

A number of in vitro effects of (S)-canadine have been reported. It stimulates myogenesis and inhibits muscle protein degradation. [7] (S)-Canadine blocks K(ATP) channels in dopamine neurons. [8] [9] (S)-Canadine has displayed antioxidant activity: though it lacked any demonstrable cytotoxic effect in three unique cell cultures, it was observed to possess antioxidant activity against free radical-induced oxidative injury. [10] [11] (S)-Canadine can block voltage-dependent calcium channels, but at a level significantly lower than that of verapamil. [12]

CPU 86017

CPU 86017 [149088-32-4] CPU 86017.svg
CPU 86017 [149088-32-4]

Canadine is also used in the synthesis of CPU 86017 (a novel Class III antiarrhythmic agent with multiple actions at ion channels). [13]

References

  1. 1 2 Hagel, Jillian M.; Morris, Jeremy S.; Lee, Eun-Jeong; Desgagne-Penix, Isabel; Bross, Crystal D.; Chang, Limei; Chen, Xue; Farrow, Scott C.; Zhang, Ye (2015). "Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants". BMC Plant Biology. 15 (1): 227. Bibcode:2015BMCPB..15..227H. doi: 10.1186/s12870-015-0596-0 . PMC   4575454 . PMID   26384972.
  2. ↑ Dang, Thu-Thuy T.; Facchini, Peter J. (2014). "CYP82Y1 is N-Methylcanadine 1-Hydroxylase, a Key Noscapine Biosynthetic Enzyme in Opium Poppy" (PDF). The Journal of Biological Chemistry. 289 (4): 2013–2026. doi: 10.1074/jbc.M113.505099 . PMC   3900951 . PMID   24324259.
  3. ↑ Chen, Xue; Facchini, Peter J. (2014). "Short-chain dehydrogenase/reductase catalyzing the final step of noscapine biosynthesis is localized to laticifers in opium poppy". The Plant Journal. 77 (2): 173–184. Bibcode:2014PlJ....77..173C. doi: 10.1111/tpj.12379 . PMID   24708518.
  4. ↑ Weber HA, Zart MK, Hodges AE, et al. (December 2003). "Chemical comparison of goldenseal (Hydrastis canadensis L.) root powder from three commercial suppliers". Journal of Agricultural and Food Chemistry. 51 (25): 7352–8. Bibcode:2003JAFC...51.7352W. doi:10.1021/jf034339r. PMID   14640583.
  5. ↑ Bauer W, Zenk MH (1991). "Formation of (R)-configurated tetrahydroprotoberberine alkaloids in vivo and in vitro". Tetrahedron Lett. 32 (4): 487–490. doi:10.1016/S0040-4039(00)79475-5.
  6. ↑ Bitchagno, Gabin Thierry M.; Nchiozem-Ngnitedem, Vaderament-A.; Melchert, Dennis; Fobofou, Serge Alain (2022). "Demystifying racemic natural products in the homochiral world". Nature Reviews Chemistry. 6 (11): 806–822. doi:10.1038/s41570-022-00431-4. PMC   9562063 .
  7. ↑ Lee, Hyejin; Lee, Sang-Jin; Bae, Gyu-Un; Baek, Nam-In; Ryu, Jae-Ha (2017). "Canadine from Corydalis turtschaninovii Stimulates Myoblast Differentiation and Protects against Myotube Atrophy". International Journal of Molecular Sciences. 18 (12): 2748. doi: 10.3390/ijms18122748 . PMC   5751347 . PMID   29258243.
  8. ↑ Wu, Chen; Yang, Kechun; Liu, Qiang; Wakui, Matoko; Jin, Guo-zhang; Zhen, Xuechu; Wu, Jie (2010). "Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta". Neuropharmacology. 59 (7–8): 567–72. doi:10.1016/j.neuropharm.2010.08.018. PMID   20804776. S2CID   27386799.
  9. ↑ Wu, Jie; Jin, Guo Zhang (1997). "Tetrahydroberberine blocks membrane K+ channels underlying its inhibition of intracellular message-mediated outward currents in acutely dissociated CA1 neurons from rat hippocampus". Brain Research. 775 (1–2): 214–8. doi:10.1016/s0006-8993(97)00960-8. PMID   9439847. S2CID   42250453.
  10. ↑ Correché, Estela R.; Andujar, Sebastian A.; Kurdelas, Rita R.; Lechón, María J. Gómez; Freile, Mónica L.; Enriz, Ricardo D. (2008). "Antioxidant and cytotoxic activities of canadine: Biological effects and structural aspects". Bioorganic & Medicinal Chemistry. 16 (7): 3641–51. doi:10.1016/j.bmc.2008.02.015. PMID   18295494.
  11. ↑ Mari, Giacomo; Catalani, Simona; Antonini, Elena; De Crescentini, Lucia; Mantellini, Fabio; Santeusanio, Stefania; Lombardi, Paolo; Amicucci, Antonella; Battistelli, Serafina (2018). "Synthesis and biological evaluation of novel heteroring-annulated pyrrolino-tetrahydroberberine analogues as antioxidant agents". Bioorganic & Medicinal Chemistry. 26 (18): 5037–44. doi:10.1016/j.bmc.2018.08.038. PMID   30196978. S2CID   52177815.
  12. ↑ Yang, S; Miao, Y.S.; Han, Q; Jiang, M.H.; Jin, G.Z. (1993). "Effects of (-)-stepholidine and tetrahydroberberine on high potassium-evoked contraction and calcium influx in rat artery". Zhongguo Yao Li Xue Bao. 14 (3): 235–7. PMID   8237399.
  13. ↑ Dai, De-Zai (2006). "CPU86017: a novel Class III antiarrhythmic agent with multiple actions at ion channels". Cardiovascular Drug Reviews. 24 (2): 101–115. doi:10.1111/j.1527-3466.2006.00101.x. ISSN   0897-5957. PMID   16961724.
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