Enantioselective Total Synthesis of (+)‐Eucophylline

The total enantioselective synthesis of (+)‐eucophylline 1 was achieved using as a key‐structural motif a chiral piperidinone bearing the natural product all‐carbon quaternary stereocenter. The elaboration of the latter is based on two strategies relying on the free‐radical carbo‐cyanation and sulfo...

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Veröffentlicht in:Chemistry : a European journal 2022-03, Vol.28 (16), p.e202200088-n/a
Hauptverfasser: Traboulsi, Iman, Dange, Nitin S., Pirenne, Vincent, Robert, Frédéric, Landais, Yannick
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container_issue 16
container_start_page e202200088
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creator Traboulsi, Iman
Dange, Nitin S.
Pirenne, Vincent
Robert, Frédéric
Landais, Yannick
description The total enantioselective synthesis of (+)‐eucophylline 1 was achieved using as a key‐structural motif a chiral piperidinone bearing the natural product all‐carbon quaternary stereocenter. The elaboration of the latter is based on two strategies relying on the free‐radical carbo‐cyanation and sulfonyl‐cyanation respectively of enantiopure substituted cyclopropenes and cyclobutenes. Co‐ or Ni‐boride reduction of the nitrile functional group along with the cyclopropane and cyclobutane ring‐opening then led to the formation of the chiral piperidinone ring. Further elaboration of the latter into the key 1‐azabicyclo[3.3.1]nonane motif followed by its coupling with a 2‐cyanoaniline allowed the formation of the tetrahydrobenzo[b][1,8]‐naphthyridine skeleton of 1, which was finally accessible in 17 steps and 5.9 % overall yield from 1,1‐dibromobutene. Two strategies based respectively on the free‐radical carbo‐ and sulfonyl‐cyanation of cyclopropenes and cyclobutenes were developed to achieve the total enantioselective synthesis of (+)‐eucophylline, a monoterpene alkaloid isolated from Leuconotis eugenifolius.
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subjects Azabicyclo Compounds - chemistry
Chemical Sciences
Chemistry
Cyclobutane
Cyclobutanes - chemistry
cyclobutene
Cyclopropane
Enantiomers
Eucophylline
Free Radicals
Functional groups
Monoterpene indole Alkaloid
Natural products
Organic chemistry
Organic compounds
radical
Stereoisomerism
sulfonyl-cyanation
Synthesis
title Enantioselective Total Synthesis of (+)‐Eucophylline
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