Protopine

Protopine ^[1]

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
CAS Number	130-86-9  Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:16415  Y
ChEMBL	ChEMBL453019  Y
ChemSpider	4799  Y
ECHA InfoCard	100.004.546
EC Number	204-999-6
KEGG	C05189  Y
PubChem CID	4970
UNII	UIW569HT35  Y
CompTox Dashboard (EPA)	DTXSID90156282
InChI 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 Y Key: GPTFURBXHJWNHR-UHFFFAOYSA-N Y
SMILES c15cc3OCOc3cc5CCN(C)Cc2c(CC1=O)ccc4c2OCO4
Properties
Chemical formula	C20H19NO5
Molar mass	353.369 g/mol
Appearance	white crystals
Density	1.399 g/cm3
Melting point	208 °C (406 °F; 481 K)
Solubility in water	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). Infobox references

Protopine is an alkaloid occurring in opium poppy, ^[2] Corydalis tubers ^[3] 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. ^{[5] [6]}

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: ^{[8] [9]}

(S)-cis-N-methylstylopine

+ NADPH

 

 

O₂

H₂O

 

 

 

protopine

+ NADP+

 

Metabolism

The enzyme protopine 6-monooxygenase converts protopine into dihydrosanguinarine. ^{[8] [10]} NADP⁺ and water are the by-products.

protopine

+ NADPH

 

 

O₂

H₂O

 

 

 

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

• Cryptopine
• Bürgi-Dunitz angle

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.