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Synthesis and Antileishmanial Activity of Indoloquinones Containing a Fused Benzothiazole Ring
Author(s) -
Tapia Ricardo A.,
Prieto Yolanda,
Pautet Félix,
Domard Monique,
Sarciron MarieElizabeth,
Walchshofer Nadia,
Fillion Houda
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200212)2002:23<4005::aid-ejoc4005>3.0.co;2-l
Subject(s) - chemistry , benzothiazole , stereochemistry , thiazole , alkylation , lithium aluminium hydride , dept , medicinal chemistry , organic chemistry , catalysis
Pyrazinoindoloquinone 6 was synthesized by alkylation of ethyl 4,7‐dimethoxyindole‐2‐carboxylate ( 1 ), followed by cyclization of the N ‐bromoethyl derivative 2b in the presence of ammonia. Oxidative demethylation of 2b and of the oxopyrazinoindole 3 with silver( II ) oxide furnished quinones 5b and 6 . Reduction of 3 with lithium aluminium hydride in dioxane provided 4 , which was oxidized to afford 7 . Quinones 5b , 6 , and 7 were then treated in situ with the thiazole o ‐quinodimethane 9 to afford regioisomeric mixtures of the tetracyclic quinones 10 or the pentacyclic derivatives 11 or 12 . The structural assignment was made by 2D NMR 1 H‐ 13 C HMBC correlation performed on the major regioisomer 10a . In vitro antileishmanial assays showed that dimethoxyindole 2a and quinones 12a + 12b possess good inhibitory activity against two Leishmania sp. without any cytotoxicity towards a THP‐1 cell line. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)