Synthesis of a regioisomeric analogue of the 3C-protease inhibitor thysanone via a Hauser annulation strategy

Autor:	Scott I. Houghton, Paul D. Woodgate, Margaret A. Brimble
Rok vydání:	2007
Předmět:	chemistry.chemical_classification Annulation Ketone Stereochemistry Organic Chemistry Biochemistry Naphthoquinone chemistry.chemical_compound Wacker process chemistry Drug Discovery Ethyl acrylate 3c protease Lactone Diels–Alder reaction
Zdroj:	Tetrahedron. 63:880-887
ISSN:	0040-4020
Popis:	Hauser annulation of 3-cyano-5,7-dimethoxy-(3H)-isobenzofuran-1-one 4 with ethyl acrylate as a method to access activated naphthoquinone 3, a key intermediate for the synthesis of thysanone 1, proved unreliable. In contrast to this, Hauser annulation of regioisomeric 3-cyano-4,6-dimethoxy-(3H)-isobenzofuran-1-one 13 with ethyl acrylate proceeded readily affording ethyl 5,7-dimethoxy-1,4-naphthoquinone 12, after oxidation of the initial dihydroxynaphthalene 16. Allylation of naphthoquinone 12 followed by reductive methylation and Wacker oxidation afforded ketone 11 that underwent CBS reduction to (2′S)-alcohol 19 followed by cyclisation to lactone 20. Reduction of the lactone followed by oxidative demethylation afforded (1S,3S)-6,8-dimethoxy-1-hydroxy-3-methylpyrano[2,3-c]-1,4-naphthoquinone 22, a regioisomeric analogue of the 3C-protease inhibitor thysanone 1.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::d801ebeb48095a0e704cff5b90710b3c https://doi.org/10.1016/j.tet.2006.11.046 Zobrazit plný text záznamu Full Text from ScienceDirect