Tetrahydrocoptisine

Tetrahydrocoptisine

(S)-tetrahydrocoptisine
Names
IUPAC name 5,7,17,19-tetraoxa-13-azahexacyclo[11.11.0.02,10.04,8.015,23.016,20]tetracosa-2,4(8),9,15(23),16(20),21-hexaene
Other names Stylopine
Identifiers
CAS Number	84-39-9  Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:18285
ChemSpider	389482
KEGG	C05175  Y
PubChem CID	440583
UNII	J0JS75Q12Z  Y
CompTox Dashboard (EPA)	DTXSID50904180
InChI InChI=1S/C19H17NO4/c1-2-16-19(24-10-21-16)14-8-20-4-3-12-6-17-18(23-9-22-17)7-13(12)15(20)5-11(1)14/h1-2,6-7,15H,3-5,8-10H2/t15-/m0/s1 Y Key: UXYJCYXWJGAKQY-HNNXBMFYSA-N Y
SMILES c1cc2c(c3c1C[C@H]1c4cc5c(cc4CCN1C3)OCO5)OCO2
Properties
Chemical formula	C19H17NO4
Molar mass	323.348 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Tetrahydrocoptisine (also known as stylopine) is an alkaloid isolated from Corydalis species. ^{[1] [2]}

Biosynthesis

The (S)-isomer of tetrahydrocoptisine is produced when the enzyme (S)-stylopine synthase acts on (S)-cheilanthifoline to form a second methylenedioxy ring: ^{[2] [3]}

cheilanthifoline

+ NADPH

 

 

O₂

2 H₂O

 

 

 

(S)-tetrahydrocoptisine

+ NADP⁺

 

Metabolism

Tetrahydrocoptisine is converted to coptisine by an oxidation reaction catalysed by the enzyme tetrahydroberberine oxidase. ^{[2] [4]}

tetrahydrocoptisine

+ H⁺

 

 

2 O₂

2 H₂O₂

 

 

 

coptisine

Alternatively, it can be converted into protopine in two steps. The first is a methylation reaction by the enzyme (S)-tetrahydroprotoberberine N-methyltransferase using the cofactor, S-adenosyl methionine (SAM). This transfers a methyl group, giving S-adenosyl-L-homocysteine (SAH). ^{[2] [5]}

(S)-tetrahydrocoptisine

+ SAM

 

 

 

 

 

 

 

(S)-cis-N-methylstylopine

+ SAH

 

Then the product, (S)-cis-N-methylstylopine, is oxidised by the enzyme methyltetrahydroprotoberberine 14-monooxygenase: ^{[2] [6]}

(S)-cis-N-methylstylopine

+ NADPH

 

 

O₂

H₂O

O₂

H₂O

 

protopine

+ NADP+

 

References

1. Li, W.; Huang, H.; Zhang, Y.; Fan, T.; Liu, X.; Xing, W.; Niu, X. (2013). "Anti-inflammatory effect of tetrahydrocoptisine from Corydalis impatiens is a function of possible inhibition of TNF-α, IL-6 and NO production in lipopolysaccharide-stimulated peritoneal macrophages through inhibiting NF-κB activation and MAPK pathway". European Journal of Pharmacology. 715 (1–3): 62–71. doi:10.1016/j.ejphar.2013.06.017. PMID   23810685.
2. 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.
3. Bauer W, Zenk MH (1991). "Two methylenedioxy bridge-forming cytochrome P-450 dependent enzymes are involved in (S)-stylopine biosynthesis". Phytochemistry . 30 (9): 2953–2961. Bibcode:1991PChem..30.2953B. doi:10.1016/S0031-9422(00)98230-X.
4. "Coptisine biosynthesis". PubChem. Retrieved 2026-02-06.
5. Rueffer M, Zumstein G, Zenk MH (1990). "Partial purification and characterization of S-adenosyl-L-methionine:(S)-tetrahydroprotoberberine cis-N-methyltransferase from suspension-cultured cells of Eschscholtzia and Corydalis" (PDF). Phytochemistry . 29 (12): 3727–3733. doi:10.1016/0031-9422(90)85321-6.
6. 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.