delphinine
{{chembox
| Watchedfields = changed
| verifiedrevid = 443565206
| ImageFile1 =Delphinine.svg
| ImageSize1 =
| ImageFile2 =Delphinine.png
| ImageSize2 =
| IUPACName =
| OtherNames =8-(Acetyloxy)-13-hydroxy-1,6,16-trimethoxy-4-(methoxymethyl)-20-methylaconitan-14-yl benzoate
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 390329
| InChI = 1/C33H45NO9/c1-18(35)43-32-15-22(40-5)31(37)14-20(23(32)28(31)42-29(36)19-10-8-7-9-11-19)33-21(39-4)12-13-30(17-38-3)16-34(2)27(33)24(32)25(41-6)26(30)33/h7-11,20-28,37H,12-17H2,1-6H3/t20-,21+,22+,23-,24+,25+,26-,27?,28-,30+,31+,32-,33+/m1/s1
| InChIKey = REVYTWNGZDPRKE-UWZYQZSNBH
| SMILES1 = O=C(O[C@H]5[C@]3(O)C[C@H]4[C@@]16C2N(C)C[C@]([C@H]1[C@@H](OC)[C@@H]2[C@@](OC(=O)C)(C[C@@H]3OC)[C@H]45)(COC)CC[C@@H]6OC)c7ccccc7
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C33H45NO9/c1-18(35)43-32-15-22(40-5)31(37)14-20(23(32)28(31)42-29(36)19-10-8-7-9-11-19)33-21(39-4)12-13-30(17-38-3)16-34(2)27(33)24(32)25(41-6)26(30)33/h7-11,20-28,37H,12-17H2,1-6H3/t20-,21+,22+,23-,24+,25+,26-,27?,28-,30+,31+,32-,33+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = REVYTWNGZDPRKE-UWZYQZSNSA-N
| CASNo_Ref = {{cascite|correct|??}}
| CASNo =561-07-9
| PubChem =441726
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = IN41I78D7R
| SMILES =CC(=O)O[C@]12C[C@@H]([C@]3(C[C@H]([C@@H]1[C@H]3OC(=O)C4=CC=CC=C4)[C@]56[C@H](CC[C@@]7([C@H]5[C@H]([C@H]2C6N(C7)C)OC)COC)OC)O)OC
}}
|Section2={{Chembox Properties
| Formula =C33H45NO9
| MolarMass =599.712
| Appearance =colorless solid
| Density =
| MeltingPtC = 197 to 199
| MeltingPt_notes =
| BoilingPt =
| Solubility =
}}
|Section3={{Chembox Hazards
| MainHazards =Toxic
| FlashPt =
| AutoignitionPt =
}}
}}
Delphinine is a toxic diterpenoid alkaloid found in plants from the Delphinium (larkspur) and Atragene (a clematis) genera, both in the family Ranunculaceae.{{cite book | title = Phytochemical Dictionary | veditors = Harbourne JB, Baxter H | date = 1993 | page = 148 | location = London | publisher = Taylor & Francis }} Delphinine is the principal alkaloid found in Delphinium staphisagria seeds – at one time, under the name stavesacre, a very well known herbal treatment for body lice.{{Cite web | url=http://www.botanical.com/botanical/mgmh/s/stavas90.html |title = A Modern Herbal | Stavesacre}} It is related in structure and has similar effects to aconitine, acting as an allosteric modulator of voltage gated sodium channels,{{cite journal | vauthors = Turabekova MA, Rasulev BF, Levkovich MG, Abdullaev ND, Leszczynski J | title = Aconitum and Delphinium sp. alkaloids as antagonist modulators of voltage-gated Na+ channels. AM1/DFT electronic structure investigations and QSAR studies | journal = Computational Biology and Chemistry | volume = 32 | issue = 2 | pages = 88–101 | date = April 2008 | pmid = 18201930 | pmc = 5001567 | doi = 10.1016/j.compbiolchem.2007.10.003 }} and producing low blood pressure, slowed heart rate and abnormal heart rhythms. These effects make it highly poisonous ({{LD50}} 1.5–3.0 mg/kg in rabbit and dog; frogs are ~10x more susceptible).{{cite journal | vauthors = Benn MH, Jacyno JM | date = 1983 | title = Chapter 4 | journal = The Alkaloids: Chemical and Biological Perspectives | volume = 1 | veditors = Pelletier SW | pages = 153–210 | location = New York | publisher = Wiley }} While it has been used in some alternative medicines (e.g. in herbal medicine{{cite journal | vauthors = Desai HK, Hart BP, Caldwell RW, Jianzhong-Huang JH, Pelletier SW | title = Certain norditerpenoid alkaloids and their cardiovascular action | journal = Journal of Natural Products | volume = 61 | issue = 6 | pages = 743–8 | date = June 1998 | pmid = 9644057 | doi = 10.1021/np970499j | bibcode = 1998JNAtP..61..743D }}{{cite journal | vauthors = Díaz JG, Ruiz JG, de La Fuente G | title = Alkaloids from Delphinium staphisagria | journal = Journal of Natural Products | volume = 63 | issue = 8 | pages = 1136–9 | date = August 2000 | pmid = 10978212 | doi = 10.1021/np990453l | bibcode = 2000JNAtP..63.1136D }}), most of the medical community does not recommend using it due to its extreme toxicity.
Isolation
One of the earliest reports of the isolation of delphinine, from D. staphisagria, was that of the French chemists Lassaigne and Feneulle, in 1819.{{cite journal | vauthors = Lassaigne JL, Feneulle H | title = Analyse de la staphisaigre. | journal = Ann. Chim. Phys. |series=Série 2 | date = 1819 | volume = 12 | pages = 358–71 }} A less antique and more accessible report is that of the USDA chemist L. N. Markwood, who also briefly reviewed the earlier isolation work.{{cite journal | vauthors = Markwood LN | title = Isolation of the oil and alkaloids of stavesacre seed.(Delphinium staphisagria). | journal = Journal of the American Pharmaceutical Association | date = October 1927 | volume = 16 | issue = 10 | pages = 928–32 | doi = 10.1002/jps.3080161006 }} Notably, these early isolations were carried out without the aid of chromatography, since delphinine crystallizes readily from a petroleum ether extract after the typical acid-base cycling used in traditional plant alkaloid-extraction methods.{{cite journal | vauthors = Jacobs WA, Craig LC | title = DELPHININE | journal = Journal of Biological Chemistry | date = February 1939 | volume = 127 | issue = 2 | pages = 361–6 | doi = 10.1016/S0021-9258(18)73787-3 | doi-access = free }}
Chemistry
Despite the relative ease of isolation and early discovery of delphinine, its molecular structure was not established in its currently accepted form until the early 1970s. At that time, Wiesner's research group corrected the stereochemistry of the methoxy group at C-1 from the β- to the α- configuration.{{cite journal | vauthors = Aneja R, Locke DM, Pelletier SW | title = The diterpene alkaloids: the structure and stereochemistry of heteratisine. | journal = Tetrahedron | date = January 1973 | volume = 29 | issue = 21 | pages = 3297–308 | doi = 10.1016/S0040-4020(01)93482-9 }}{{cite book | vauthors = Pelletier SW, Wright LH | title = Alkaloids | chapter = Recent developments in diterpenoid alkaloids chemistry | volume = 2 | date = January 1972 | pages = 247–258 (254–255) | location = London | publisher = The Chemical Society | doi = 10.1039/9781847555588-00247 | isbn = 978-0-85186-267-5 }} Thus, any drawing of the delphinine molecule appearing before 1971–1972 is likely to show the incorrect stereochemistry at C-1.
Pharmacology
As a result of its early discovery and isolation in crystalline form (then considered a criterion of purity), the pharmacological properties of delphinine were extensively investigated in the 19th century, despite the fact that its molecular structure was unknown. It is likely that some of these investigations were carried out with impure drug and should be interpreted with caution. References to and commentary on these early studies may be found in the review by Benn and Jacyno. More recent studies focused on the cardiovascular toxicity of delphinine.{{cite journal | vauthors = Scherf D, Blumenfeld S, Tander D, Yildiz M | title = The effect of diphenylhydantoin (Dilantin) sodium on atrial flutter and fibrillation provoked by focal application of a conitine or delphinine | journal = American Heart Journal | volume = 60 | pages = 936–47 | date = December 1960 | issue = 6 | pmid = 13747515 | doi = 10.1016/0002-8703(60)90125-3 }}{{cite book | vauthors = Scherf D, Schott A | date = 1973 | title = Extrasystoles and Allied Arrhythmias | edition = 2nd | location = London | publisher = Heinemann }}
In general, the pharmacology of delphinine seems to resemble that of aconitine, although the acute toxicity of delphinine appears to be lower than that of aconitine in test animals.