“Hydrastine”的意思、由来-开放百科全书

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

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 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

1. ^{{cite book|title=Pharmaceutical Journal;: A Weekly Record of Pharmacy and Allied Sciences|url=https://books.google.com/books?id=IusKAAAAYAAJ&pg=PA547|year=1862|publisher=J. Churchill|pages=547–}}
2. ^{{citation|title=Römpp CD|publisher=Georg Thieme Verlag|year=2006}}
3. ^{{cite journal|last1=Hope|first1=Edward|last2=Pyman|first2=Frank Lee|last3=Remfry|first3=Frederick George Percy|last4=Robinson|first4=Robert|title=XXXI.—A synthesis of hydrastine. Part I|journal=J. Chem. Soc.|volume=0|issue=0|year=1931|pages=236–247|issn=0368-1769|doi=10.1039/JR9310000236}}
4. ^{{cite journal|last1=Haworth|first1=R. D.|last2=Pinder|first2=A. R.|last3=Robinson|first3=R.|title=Synthesis of Hydrastine|journal=Nature|volume=165|issue=4196|year=1950|pages=529–529|issn=0028-0836|doi=10.1038/165529a0}}
5. ^{{cite journal|last1=Haworth|first1=Robert D.|last2=Pinder|first2=A. Reginald|title=360. A new route to the phthalide-isoquinoline bases, and a synthesis of (–)-hydrastine|journal=J. Chem. Soc.|volume=0|issue=0|year=1950|pages=1776–1780|issn=0368-1769|doi=10.1039/JR9500001776}}
6. ^{{cite journal|last1=Falck|first1=J.R.|last2=Manna|first2=Sukumar|title=An intramolecular passerini reaction: Synthesis of hydrastine.|journal=Tetrahedron Letters|volume=22|issue=7|year=1981|pages=619–620|issn=00404039|doi=10.1016/S0040-4039(01)92504-3}}

Total synthesis

References

External links