Protopine

Protopine
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 Edit this at Wikidata
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, Corydalis tubers and other plants of the family papaveraceae, like Fumaria officinalis.

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

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.

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

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 Q390706.

Protopine

+ NADP+
 

Metabolism

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

The enzyme uses reduced nicotinamide adenine dinucleotide phosphate (NADPH), and oxygen, with the initial product being 6-hydroxyprotopine.

2D representation of the chemical structure of Q390706.

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 Q27102210.

6-hydroxyprotopine

+ NADP+
 

6-hydroxyprotopine in turn spontaneously rearranges to dihydrosanguinarine:

Spontaneous conversion of 6-hydroxyprotopine to dihydrosanguinarine
Spontaneous conversion of 6-hydroxyprotopine to dihydrosanguinarine

See also

References

  1. ↑ The Merck Index (9 ed.). New Jersey: Merck & Co. 1976. p. 1023.
  2. ↑ "The Free Dictionary: Protopine". www.thefreedictionary.com.
  3. ↑ Jiang B, Cao K, Wang R (December 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 J, Vrublova E, Modriansky M, Ulrichova J (June 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 (July 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 JM, Morris JS, Lee EJ, Desgagné-Penix I, Bross CD, Chang L, et al. (September 2015). "Transcriptome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants". BMC Plant Biology. 15 (1) 227. doi:10.1186/s12870-015-0596-0. PMC 4575454. PMID 26384972.
  8. 1 2 Tian Y, Kong L, Li Q, Wang Y, Wang Y, An Z, et al. (November 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. 1 2 3 Tanahashi T, Zenk MH (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.