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A Polar Radical Pair Pathway To Assemble the Pyrimidinone Core of the HIV Integrase Inhibitor Raltegravir Potassium
Author(s) -
Pye Philip J.,
Zhong YongLi,
Jones Gavin O.,
Reamer Robert A.,
Houk Kendall N.,
Askin David
Publication year - 2008
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200703681
Subject(s) - raltegravir , pericyclic reaction , chemistry , integrase , human immunodeficiency virus (hiv) , stereochemistry , integrase inhibitor , combinatorial chemistry , biochemistry , virology , antiretroviral therapy , biology , viral load , gene
Break up to make up: Combined experimental and computational studies provide evidence that the key step in the synthesis of a novel anti‐HIV drug involves an unprecedented stepwise radical pair rearrangement mechanism in which radical fragments are held together by strong electrostatic forces (see scheme); this is favored over alternative mechanisms involving concerted pericyclic rearrangement.