Hydrastine
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Clinical data | |
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ATC code | none |
Pharmacokinetic data | |
Metabolism | Hepatic |
Excretion | Renal |
Identifiers | |
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CAS Number | 118-08-1 ![]() |
PubChem (CID) | 197835 |
ChemSpider | 171234 ![]() |
UNII | 8890V3217X ![]() |
ChEMBL | CHEMBL497942 ![]() |
ECHA InfoCard | 100.003.849 |
Chemical and physical data | |
Formula | C21H21NO6 |
Molar mass | 383.395 g/mol |
3D model (Jmol) | Interactive image |
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Hydrastine is an alkaloid which was discovered in 1851 by Alfred P. Durand.[1] Hydrolysis of hydrastine yields hydrastinine, which was patented by Bayer as a haemostatic drug[2] during the 1910s. It is present in Hydrastis canadensis (thus the name) and other plants of the Ranunculaceae family.
Total synthesis[edit]
The first attempt for the total synthesis of hydrastine was reported by Sir Robert Robinson and co-workers[3] in 1931. Following studies,[4][5] which were mostly troublesome for the synthesis of the key lactonic amide intermediate (structure 4 in Figure). 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 Flack synthesis was using a Passerini reaction to construct the lactonic amide intermediate 4.
Starting from a simple phenylbromide variant 1, alkylation reaction with lithium methylisocyanide gives the isocyanide intermediate 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 using POCl3 and then a catalyzed hydrogenation using PtO2 as the catalyst. Finally, hydrastine was synthesized by installing the N-methyl group via reductive amination reaction with formaldehyde.
References[edit]
- ^ American Journal of Pharmacy: 112, 1851 Missing or empty
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(help). - ^ Römpp CD, Georg Thieme Verlag, 2006
- ^ Hope, E.; Pyman, F. L.; Remfry, F. G. P.; Robinson, R., J. Chem. Soc. 1931, 236.
- ^ Haworth, R. D.; Pinder, A. R.; Robinson, R., Nature 1950, 165, 529.
- ^ Haworth, R. D.; Pinder, A. R., J. Chem. Soc. 1950, 1776.
- ^ Falck, J. R.; Manna, S., Tetrahedron Lett. 1981, 22, 619.
External links[edit]
Chisholm, Hugh, ed. (1911). "Hydrastine". Encyclopædia Britannica. 14 (11th ed.). Cambridge University Press. p. 34.
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