{{Chembox | ImageFile = Stylopine.svg | ImageClass = skin-invert-image | ImageCaption = (''S'')-tetrahydrocoptisine | ImageAlt = | IUPACName = 5,7,17,19-tetraoxa-13-azahexacyclo[11.11.0.0<sup>2,10</sup>.0<sup>4,8</sup>.0<sup>15,23</sup>.0<sup>16,20</sup>]tetracosa-2,4(8),9,15(23),16(20),21-hexaene | OtherNames = Stylopine |Section1={{Chembox Identifiers | CASNo = 84-39-9 | CASNo_Ref = {{cascite|correct|CAS}} | ChEBI = 18285 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = J0JS75Q12Z | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C05175 | PubChem = 440583 | ChemSpiderID = 389482 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI=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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = UXYJCYXWJGAKQY-HNNXBMFYSA-N | SMILES = c1cc2c(c3c1C[C@H]1c4cc5c(cc4CCN1C3)OCO5)OCO2 }} |Section2={{Chembox Properties | C=19 | H=17 | N=1 | O=4 | Formula = | MolarMass = | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = }} |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }}

'''Tetrahydrocoptisine''' (also known as '''stylopine''') is an alkaloid isolated from ''Corydalis'' species.<ref>{{cite journal | pmid = 23810685 | year = 2013 | last1 = Li | first1 = W. | last2 = Huang | first2 = H. | last3 = Zhang | first3 = Y. | last4 = Fan | first4 = T. | last5 = Liu | first5 = X. | last6 = Xing | first6 = W. | last7 = Niu | first7 = X. | title = 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 | journal = European Journal of Pharmacology | volume = 715 | issue = 1–3 | pages = 62–71 | doi = 10.1016/j.ejphar.2013.06.017 }}</ref><ref name=NPR>{{cite journal |last1=Tian |first1=Ya |last2=Kong |first2=Lingzhe |last3=Li |first3=Qi |last4=Wang |first4=Yifan |last5=Wang |first5=Yongmiao |last6=An |first6=Zhoujie |last7=Ma |first7=Yuwei |last8=Tian |first8=Lixia |last9=Duan |first9=Baozhong |last10=Sun |first10=Wei |last11=Gao |first11=Ranran |last12=Chen |first12=Shilin |last13=Xu |first13=Zhichao |title=Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids |journal=Natural Product Reports |date=2024 |volume=41 |issue=11 |pages=1787–1810 |doi=10.1039/D4NP00029C |pmid=39360417 }}</ref>

==Biosynthesis== The (''S'')-isomer of tetrahydrocoptisine is produced when the enzyme (S)-stylopine synthase acts on (''S'')-cheilanthifoline to form a second methylenedioxy ring:<ref name=NPR/><ref>{{cite journal | vauthors = Bauer W, Zenk MH | date = 1991 | title = Two methylenedioxy bridge-forming cytochrome P-450 dependent enzymes are involved in (S)-stylopine biosynthesis | journal = Phytochemistry | volume = 30 | pages = 2953&ndash;2961 | doi = 10.1016/S0031-9422(00)98230-X | issue = 9 | bibcode = 1991PChem..30.2953B }}</ref>

{{chemrxn|width=55%| {{chemrxn/cpd|cheilanthifoline }} {{chemrxn/txt|+ NADPH }} {{chemrxn/arw||fwd_in={{chem2|O2}}|fwd_out={{chem2|2 H2O}} }} {{chemrxn/cpd|qid=Q27102969|caption=(''S'')-tetrahydrocoptisine }} {{chemrxn/txt|+ NADP<sup>+</sup>}} }}

==Metabolism== Tetrahydrocoptisine is converted to coptisine by an oxidation reaction catalysed by the enzyme tetrahydroberberine oxidase.<ref name=NPR/><ref>{{cite web |title=Coptisine biosynthesis |website=PubChem |url=https://pubchem.ncbi.nlm.nih.gov/pathway/PlantCyc:PLANT_PWY-8030 |access-date=2026-02-06}}</ref>

{{chemrxn|width=45%| {{chemrxn/cpd|qid=Q27102969|caption=tetrahydrocoptisine }} {{chemrxn/txt|+ {{chem2|H+}} }} {{chemrxn/arw|fwd_in={{chem2|2 O2}}|fwd_out={{chem2|2 H2O2}} }} {{chemrxn/cpd|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).<ref name=NPR/><ref>{{cite journal |vauthors=Rueffer M, Zumstein G, Zenk MH | date = 1990 | title = Partial purification and characterization of S-adenosyl-L-methionine:(S)-tetrahydroprotoberberine cis-N-methyltransferase from suspension-cultured cells of Eschscholtzia and Corydalis | journal = Phytochemistry | volume = 29 | pages = 3727&ndash;3733 | doi = 10.1016/0031-9422(90)85321-6 | issue = 12 | url = https://epub.ub.uni-muenchen.de/3618/1/003.pdf }}</ref>

{{chemrxn|width=60%| {{chemrxn/cpd|qid=Q27102969|caption=(''S'')-tetrahydrocoptisine }} {{chemrxn/txt|+ SAM }} {{chemrxn/arw|direction=reversible }} {{chemrxn/cpd|qid=Q27105298|caption=(''S'')-''cis''-N-methylstylopine }} {{chemrxn/txt|+ SAH }} }}

Then the product, (''S'')-''cis''-N-methylstylopine, is oxidised by the enzyme methyltetrahydroprotoberberine 14-monooxygenase:<ref name=NPR/><ref>{{cite journal |vauthors=Rueffer M, Zenk MH | date = 1987 |title=Enzymatic formation of protopines by a microsomal cytochrome-P-450 system of Corydalis vaginans |journal=Tetrahedron Lett. |volume=28 |pages=5307–5310 |doi=10.1016/S0040-4039(00)96715-7 |issue=44 |url=http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-3622-0 }}</ref>

{{chemrxn|width=60%| {{chemrxn/cpd|qid=Q27105298|caption=(''S'')-''cis''-N-methylstylopine }} {{chemrxn/txt|+ NADPH }} {{chemrxn/arw|fwd_in={{chem2|O2}}|fwd_out={{chem2|H2O}} }} {{chemrxn/cpd|protopine }} {{chemrxn/txt|+ NADP+ }} }}

==References== {{reflist}}

Category:Methylenedioxyphenethylamines Category:5,6,7,8-Tetrahydro-(1,3)dioxolo(4,5-g)isoquinolines Category:Tetrahydroisoquinoline alkaloids Category:Heterocyclic compounds with 6 rings