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.
^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)
^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.
^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.
^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.
^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.
hydrastine, isoquinoline, alkaloid, which, discovered, 1851, alfred, durand, hydrolysis, hydrastine, yields, hydrastinine, which, patented, bayer, haemostatic, drug, during, 1910s, present, hydrastis, canadensis, thus, name, other, plants, family, ranunculacea. 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 HydrastineClinical dataATC codenonePharmacokinetic dataMetabolismHepaticExcretionRenalIdentifiersIUPAC 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 oneCAS Number118 08 1 YPubChem CID197835ChemSpider171234 YUNII8890V3217XChEMBLChEMBL497942 NCompTox Dashboard EPA DTXSID9025409ECHA InfoCard100 003 849Chemical and physical dataFormulaC 21H 21N O 6Molar mass383 400 g mol 13D model JSmol Interactive imageMelting point132 C 270 F SMILES O C2O C H c1ccc OC c OC c12 C H 5N C CCc4c5cc3OCOc3c4InChI 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 N Y what is this verify Contents 1 Total synthesis 2 See also 3 References 4 External linksTotal synthesis editThe 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 nbsp 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 editBicuculline 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 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint date and year link Rompp 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 ISSN 0368 1769 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 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 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 External links editChisholm Hugh ed 1911 Hydrastine Encyclopaedia Britannica Vol 14 11th ed Cambridge University Press p 34 Retrieved from https en wikipedia org w index php title Hydrastine amp oldid 1218993925, wikipedia, wiki, book, books, library,
