Hydrastine

Hydrastine is an isoquinoline 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 family Ranunculaceae.

Hydrastine
Clinical data
ATC code
  • none
Pharmacokinetic data
MetabolismHepatic
ExcretionRenal
Identifiers
IUPAC name
  • 6,7-Dimethoxy-3-(6-methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-2-benzofuran-1(3H)-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.003.849
Chemical and physical data
FormulaC21H21NO6
Molar mass383.400 g·mol−1
3D model (JSmol)
Melting point132 °C (270 °F)
SMILES
  • O=C2O[C@@H](c1ccc(OC)c(OC)c12)[C@@H]5N(C)CCc4c5cc3OCOc3c4
InChI
  • InChI=1S/C21H21NO6/c1-22-7-6-11-8-15-16(27-10-26-15)9-13(11)18(22)19-12-4-5-14(24-2)20(25-3)17(12)21(23)28-19/h4-5,8-9,18-19H,6-7,10H2,1-3H3/t18-,19+/m1/s1 Y
  • Key:JZUTXVTYJDCMDU-MOPGFXCFSA-N Y
 NY (what is this?)  (verify)

Total synthesis

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] 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 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.

See also

References

  1. 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–.{{cite journal}}: CS1 maint: date and year (link)
  2. Römpp CD, Georg Thieme Verlag, 2006
  3. 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. ISSN 0368-1769.
  4. Haworth RD, Pinder AR, Robinson R (1950). "Synthesis of Hydrastine". Nature. 165 (4196): 529. Bibcode:1950Natur.165..529H. doi:10.1038/165529a0. ISSN 0028-0836. S2CID 4198366.
  5. 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. ISSN 0368-1769.
  6. 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. ISSN 0040-4039.
  • Chisholm, Hugh, ed. (1911). "Hydrastine" . Encyclopædia Britannica. Vol. 14 (11th ed.). Cambridge University Press. p. 34.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.