hydrastine hydrastine hydrastine is an isoquinoline alkaloid which was discovered in 1851 by alfred p. durand. hydrolysis of hydrastine yields hydrastinine, which was patented by bayer as a haemostatic drug during the 1910s. it is present in hydrastis canadensis (thus the name) and other plants of the family ranunculaceae. hydrastineclinical dataatc codenonepharmacokinetic datametabolismhepaticexcretionrenalidentifiers iupac name 6,7-dimethoxy-3-(6-methyl-5,6,7,8-tetrahydrodioxoloisoquinolin-5-yl)-2-benzofuran-1(3h)-one cas number118-08-1 ypubchem cid197835chemspider171234 yunii8890v3217xchemblchembl497942 ncomptox dashboard (epa)dtxsid9025409 echa infocard100.003.849 chemical and physical dataformulac21h21no6molar mass383.400 g·mol−13d model (jsmol)interactive imagemelting point132 °c (270 °f) smiles o=c2o(c1ccc(oc)c(oc)c12)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 ykey: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 in 1931. following studies 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 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.