Article · Wikipedia archive · Last revised Jun 14, 2026

Protopine

Protopine is an alkaloid occurring in opium poppy, Corydalis tubers and other plants of the family papaveraceae, like Fumaria officinalis.

Last revised
Jun 14, 2026
Read time
≈ 2 min
Length
559 w
Citations
12
Source
Wikipedia ↗
Protopine1
source ↗
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Names
IUPAC name
7-Methyl-2′H,2′′H-7,13a-secobis([1,3]dioxolo)[4′,5′:2,3;4′′,5′′:9,10]berbin-13a-one
Systematic IUPAC name
5-Methyl-4,6,7,14-tetrahydro-2H,10H-bis([1,3]benzodioxolo)[4,5-c:5′,6′-g]azecin-13(5H)-one
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.004.546
EC Number
  • 204-999-6
KEGG
UNII
  • InChI=1S/C20H19NO5/c1-21-5-4-13-7-18-19(25-10-24-18)8-14(13)16(22)6-12-2-3-17-20(15(12)9-21)26-11-23-17/h2-3,7-8H,4-6,9-11H2,1H3 checkY
    Key: GPTFURBXHJWNHR-UHFFFAOYSA-N checkY
  • c15cc3OCOc3cc5CCN(C)Cc2c(CC1=O)ccc4c2OCO4
Properties
C20H19NO5
Molar mass 353.369 g/mol
Appearance white crystals
Density 1.399 g/cm3
Melting point 208 °C (406 °F; 481 K)
practically insoluble
Solubility in chloroform 1:15
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Protopine is an alkaloid occurring in opium poppy,2 Corydalis tubers3 and other plants of the family papaveraceae, like Fumaria officinalis.4

It has been found to inhibit histamine H1 receptors and platelet aggregation, and acts as an analgesic.56

Biosynthesis

Protopine is derived in the plants such as the opium poppy, Papaver somniferum, from the benzylisoquinoline alkaloid (S)-reticuline through a progressive series of five enzymatic transformations: 1) berberine bridge enzyme to (S)-scoulerine; 2) (S)-cheilanthifoline synthase/CYP719A25 to (S)-cheilanthifoline; 3)  (S)-stylopine synthase/CYP719A20 to (S)-stylopine; 4) (S)-tetrahydroprotoberberine N-methyltransferase to (S)-cis-N-methylstylopine.7

The final step is oxidation by the enzyme methyltetrahydroprotoberberine 14-monooxygenase:89

2D representation of the chemical structure of Q27105298.
(S)-cis-N-methylstylopine
+ NADPH
 
 
O2
H2O
Rightward reaction arrow with minor substrate(s) from top left and minor product(s) to top right
 
 
 
2D representation of the chemical structure of protopine .
protopine
+ NADP+
 


Metabolism

The enzyme protopine 6-monooxygenase converts protopine into dihydrosanguinarine.810 NADP+ and water are the by-products.

2D representation of the chemical structure of protopine .
protopine
+ NADPH
 
 
O2
H2O
Rightward reaction arrow with minor substrate(s) from top left and minor product(s) to top right
 
 
 
2D representation of the chemical structure of dihydrosanguinarine .
dihydrosanguinarine
+ NADP+
 


The enzyme uses reduced nicotinamide adenine dinucleotide phosphate (NADPH), and oxygen, with the initial product being 6-hydroxyprotopine, which spontaneously forms dihydrosanguinarine, found in plants such as Sanguinaria canadensis.11

See also

See also

References

References

  1. The Merck Index (9 ed.). New Jersey: Merck & Co. 1976. p. 1023.
  2. The Free Dictionary: Protopine
  3. Jiang, B; Cao, K; Wang, R (2004). "Inhibitory effect of protopine on K(ATP) channel subunits expressed in HEK-293 cells". European Journal of Pharmacology. 506 (2): 93–100. doi:10.1016/j.ejphar.2004.11.004. PMID 15588728.
  4. Vrba, Jiri; Vrublova, Eva; Modriansky, Martin; Ulrichova, Jitka (2011). "Protopine and allocryptopine increase mRNA levels of cytochromes P450 1A in human hepatocytes and HepG2 cells independently of AhR". Toxicology Letters. 203 (2): 135–141. doi:10.1016/j.toxlet.2011.03.015. PMID 21419197.
  5. Saeed, SA; Gilani, AH; Majoo, RU; Shah, BH (1997). "Anti-thrombotic and anti-inflammatory activities of protopine". Pharmacological Research. 36 (1): 1–7. doi:10.1006/phrs.1997.0195. PMID 9368908.
  6. Protopine at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  7. 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: 227. doi:10.1186/s12870-015-0596-0. PMC 4575454. PMID 26384972.
  8. Tian, Ya; Kong, Lingzhe; Li, Qi; Wang, Yifan; Wang, Yongmiao; An, Zhoujie; Ma, Yuwei; Tian, Lixia; Duan, Baozhong; Sun, Wei; Gao, Ranran; Chen, Shilin; Xu, Zhichao (2024). "Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids". Natural Product Reports. 41 (11): 1787–1810. doi:10.1039/d4np00029c. PMID 39360417.
  9. Rueffer M, Zenk MH (1987). "Enzymatic formation of protopines by a microsomal cytochrome-P-450 system of Corydalis vaginans". Tetrahedron Lett. 28 (44): 5307–5310. doi:10.1016/S0040-4039(00)96715-7.
  10. Tanahashi, Takao; Zenk, Meinhart H. (1990). "Elicitor induction and characterization of microsomal protopine-6-hydroxylase, the central enzyme in benzophenanthridine alkaloid biosynthesis". Phytochemistry. 29 (4): 1113–1122. doi:10.1016/0031-9422(90)85414-B.
  11. Ignatov, Atanas; Clark, W.Gregg; Cline, Steven D.; Psenak, Mikulas; Krueger, Robert J.; Coscia, Carmine J. (1996). "Elicitation of dihydrobenzophenanthridine oxidase in Sanguinaria canadensis cell cultures". Phytochemistry. 43 (6): 1141–1144. doi:10.1016/S0031-9422(96)00540-7. PMID 8987906.