Columbamine

Columbamine
Names
	IUPAC name 3,9,10-Trimethoxy-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium-2-ol
	Other names Dehydroisocorypalmine
Identifiers
CAS Number	3621-36-1 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:15920;
ChEMBL	ChEMBL400345;
ChemSpider	65261;
KEGG	C01795;
PubChem CID	72310;
UNII	7T4808FEJW;
CompTox Dashboard (EPA)	DTXSID80189766 ;
	InChI InChI=1S/C20H19NO4/c1-23-18-5-4-12-8-16-14-10-17(22)19(24-2)9-13(14)6-7-21(16)11-15(12)20(18)25-3/h4-5,8-11H,6-7H2,1-3H3/p+1 Key: YYFOFDHQVIODOQ-UHFFFAOYSA-O;
	SMILES COC1=C(C2=C[N+]3=C(C=C2C=C1)C4=CC(=C(C=C4CC3)OC)O)OC;
Properties
Chemical formula	C20H20NO4+
Molar mass	338.382 g·mol−1
Melting point	280–282 °C (536–540 °F; 553–555 K) (chloride salt)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Columbamine is an isoquinoline alkaloid made up of four rings, two of which contain nitrogen. It is related to berberine but without its methylenedioxy group. Columbamine is also called dehydroisocorypalmine.^[2] It has usually been isolated and characterised as its chloride salt.^[1]

Occurrence

Columbamine has been found in several Berberis species, Coptis chinensis^[3] and Jateorhiza palmata.^[1]

Biosynthesis

The biosynthesis of columbamine starts with tyrosine and proceeds via (S)-reticuline in a pathway leading to benzylisoquinoline alkaloids.^[4]^[5] The final step is catalysed by the enzyme tetrahydroberberine oxidase, which oxidises (S)-isocorypalmine:^[1]^[6]

(S)-isocorypalmine

+ H⁺

2 O₂

2 H₂O₂

Rightward reaction arrow with minor substrate(s) from top left and minor product(s) to top right

columbamine

Metabolism

Columbamine is converted to berberine by the enzyme columbamine oxidase:^[7]

2 columbamine

O₂

2 H₂O

2

berberine

A methylation reaction catalysed by columbamine O-methyltransferase produces palmatine. The methyl group comes from the cofactor, S-adenosyl methionine (SAM). This enzyme was characterised from Berberis wilsoniae.^[8]

columbamine

+ SAM

palmatine

+ SAH

References

1 2 3 4 Mascavage, Linda M.; Jasmin, Serge; Sonnet, Philip E.; Wilson, Michael; Dalton, David R. (2010). "Alkaloids". Ullmann's Encyclopedia of Industrial Chemistry. p. 54. doi:10.1002/14356007.a01_353.pub2. ISBN 978-3-527-30385-4.
↑ PubChem. "Columbamine". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-04-29.
↑ Wu-Chang Chuang; Dun-Shyurng Young; Lilian Kao Liu; Shuenn-Jyi Sheu (1996). "Liquid chromatographic-electrospray mass spectrometric analysis of Coptidis Rhizoma". Journal of Chromatography A. 755: 19–26. doi:10.1016/S0021-9673(96)00591-2.
↑ 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.
↑ Begley, Tadhg P. (2009). Encyclopedia of Chemical Biology. Vol. 10. Wiley. pp. 1569–1570. doi:10.1002/cbic.200900262. ISBN 978-0-471-75477-0.
↑ Enzyme 1.3.3.8 at KEGG Pathway Database.
↑ Rueffer M, Zenk MH (1985). "Berberine synthesis, the methylenedioxy group forming enzyme in berberine synthesis". Tetrahedron Lett. 26 (2): 201–202. doi:10.1016/S0040-4039(00)61879-8.
↑ Rueffer M, Amann M, Zenk MH (1986). "S-Adenosyl-L-methionine:columbamine O-methyltransferase, a compartmentalized enzyme in protoberberine biosynthesis". Plant Cell Reports. 5 (3): 182–185. Bibcode:1986PCelR...5..182R. doi:10.1007/BF00269113. PMID 24248127.

[Ullmann-1] 1 2 3 4 Mascavage, Linda M.; Jasmin, Serge; Sonnet, Philip E.; Wilson, Michael; Dalton, David R. (2010). "Alkaloids". Ullmann's Encyclopedia of Industrial Chemistry. p. 54. doi:10.1002/14356007.a01_353.pub2. ISBN 978-3-527-30385-4.

[:0-2] PubChem. "Columbamine". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-04-29.

[3] Wu-Chang Chuang; Dun-Shyurng Young; Lilian Kao Liu; Shuenn-Jyi Sheu (1996). "Liquid chromatographic-electrospray mass spectrometric analysis of Coptidis Rhizoma". Journal of Chromatography A. 755: 19–26. doi:10.1016/S0021-9673(96)00591-2.

[4] 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.

[5] Begley, Tadhg P. (2009). Encyclopedia of Chemical Biology. Vol. 10. Wiley. pp. 1569–1570. doi:10.1002/cbic.200900262. ISBN 978-0-471-75477-0.

[KEGG-6] Enzyme 1.3.3.8 at KEGG Pathway Database.

[7] Rueffer M, Zenk MH (1985). "Berberine synthesis, the methylenedioxy group forming enzyme in berberine synthesis". Tetrahedron Lett. 26 (2): 201–202. doi:10.1016/S0040-4039(00)61879-8.

[8] Rueffer M, Amann M, Zenk MH (1986). "S-Adenosyl-L-methionine:columbamine O-methyltransferase, a compartmentalized enzyme in protoberberine biosynthesis". Plant Cell Reports. 5 (3): 182–185. Bibcode:1986PCelR...5..182R. doi:10.1007/BF00269113. PMID 24248127.

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