Open AccessToward the Total Synthesis of Alpkinidine: Synthesis of Haloquinone CE Ring System Synthons and Attempted Nucleophilic Bisannulation
Author(s) -
Marco Buccini,
Louisa Tham,
Francis Dhoro,
Brian W. Skelton,
Craig M. Williams,
Matthew Piggott
Publication year - 2022
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.2c02116
Subject(s) - synthon , regioselectivity , nucleophile , ring (chemistry) , chemistry , natural product , nucleophilic substitution , total synthesis , adduct , organic chemistry , combinatorial chemistry , stereochemistry , catalysis
Model chemistry involving the bisannulation of 2,3-dichloro-1,4-naphthoquinone with the ester enolate derived from ethyl o -nitrophenylacetic acid, which rapid assembled the ABCD ring system of a pentacyclic pyrroloacridine, has been applied to the attempted synthesis of the marine natural product alpkinidine. The reaction of ethyl o -nitrophenylacetic acid with 6,7-dichloro-2-methylisoquinoline-1,5,8(2 H )-trione, required to extend the model strategy to alpkinidine, was unfruitful, giving only complex mixtures. Efforts to direct the regiochemistry of the key Michael substitution step using 6-bromo-2-methylisoquinoline-1,5,8(2 H )-trione afforded an adduct sharing the complete carbon skeleton of alpkinidine, but this could not be elaborated to the natural product.