Hydrastine
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Metabolism | Hepatic |
Excretion | Renal |
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ECHA InfoCard | 100.003.849 |
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Formula | C21H21NO6 |
Molar mass | 383.400g·mol−1 |
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Melting point | 132 °C (270 °F) |
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Hydrastineis anisoquinolinealkaloidwhich was discovered in 1851 byAlfred P. Durand.[1]Hydrolysisof hydrastine yieldshydrastinine,which was patented byBayeras ahaemostaticdrug[2]during the 1910s. It is present inHydrastis canadensis(thus the name) and other plants of the familyRanunculaceae.
Total synthesis
[edit]The first attempt for thetotal synthesisof hydrastine was reported bySir Robert Robinsonand co-workers[3]in 1931. Following studies[4][5]where the synthesis of the key lactonic amide intermediate (structure 4 in figure) was the most troublesome, the major breakthrough was achieved in 1981 when J. R. Falck and co-workers[6]reported a four-step total synthesis of hydrastine from simple starting materials. The key step in the Falck synthesis was using aPasserini reactionto construct the lactonic amide intermediate 4.
Starting from a simple phenylbromide variant 1, alkylation reaction with lithium methylisocyanide gives theisocyanideintermediate 2. Reacting isocyanide intermediate 2 with opianic acid 3 initiated the intramolecular Passerini reaction to give the key lactonic amide intermediate 4. The tetrahydro-isoquinolin ring was formed by first a ring-closure reaction under dehydration conditions usingPOCl3and then a catalyzed hydrogenation using PtO2 as the catalyst. Finally, hydrastine was synthesized by installing the N-methyl group viareductive aminationreaction withformaldehyde.
See also
[edit]- Bicuculline(very similar in structure)
References
[edit]- ^Perrins JD (July 1862)."On Hydrastine, an Alkaloid Occurring in Hydrastis Canadensis".Pharmaceutical Journal: A Weekly Record of Pharmacy and Allied Sciences.J. Churchill: 547–.
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:CS1 maint: date and year (link) - ^Römpp CD,Georg Thieme Verlag, 2006
- ^Hope E, Pyman FL, Remfry FG, Robinson R (1931). "XXXI.—A synthesis of hydrastine. Part I".J. Chem. Soc.:236–247.doi:10.1039/JR9310000236.ISSN0368-1769.
- ^Haworth RD, Pinder AR, Robinson R (1950)."Synthesis of Hydrastine".Nature.165(4196): 529.Bibcode:1950Natur.165..529H.doi:10.1038/165529a0.ISSN0028-0836.S2CID4198366.
- ^Haworth RD, Pinder AR (1950). "360. A new route to the phthalide-isoquinoline bases, and a synthesis of (–)-hydrastine".J. Chem. Soc.:1776–1780.doi:10.1039/JR9500001776.ISSN0368-1769.
- ^Falck JR,Manna S (1981). "An intramolecular passerini reaction: Synthesis of hydrastine".Tetrahedron Letters.22(7): 619–620.doi:10.1016/S0040-4039(01)92504-3.ISSN0040-4039.
External links
[edit]- Chisholm, Hugh,ed. (1911). .Encyclopædia Britannica.Vol. 14 (11th ed.). Cambridge University Press. p. 34.