Syntheses of 2,3-Dihydro-1,4-Benzodioxins and Bioisosteres as Structural Motifs for Biologically Active Compounds

Author(s): Olga Cruz-Lopez, Maria C. Nunez, Ana Conejo-Garcia, Maria Kimatrai, Joaquin M. Campos.

Journal Name: Current Organic Chemistry

Volume 15 , Issue 6 , 2011

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Abstract:

The 2,3-dihydro-1,4-benzodioxin ring system is present in a large number of structures of therapeutic agents possessing important biological activities. Some of them are antihypertensive agents. Others are involved in nervous breakdown and schizophrenia or represent an attractive therapeutic target for the treatment of glaucoma. The 2,3-dihydro-1,4-benzodioxin core has also been developed for the synthesis of inhibitors of 5-lipoxygenase and accordingly, these 2,3-dihydro-1,4-benzodioxins are useful for the treatment of inflammatory diseases such as asthma and arthritis. The synthesis and reactivity of several bioisosteres of the non-aromatic ring will be discussed. The occurrence of the 2,3-dihydro-1,4-benzodioxin structure in various naturally abundant compounds is also known. The total synthesis of angustureine (a novel 1,2,3,4-tetrahydroquinoline alkaloid with a n-pentyl side chain at position 2) will be presented. The bioisosteric replacement of benzene by pyridine in compounds containing the 2-substituted-2,3-dihydro-1,4-benzodioxin core has yielded derivatives of biological interest in diverse therapeutic areas such as central nervous system and cardiovascular diseases. These promising results have prompted interest in the area of 1,4-dioxino-[2,3-b]pyridine analogues. Several modifications on both the aromatic and the non-aromatic rings will be reviewed, including several transformations of the new heterocycles, such as the Smiles rearrangement. Moreover, the enantiomers of 2- and 3-hydroxymethyl- 2,3-dihydro-1,4-dioxino-[2,3-b]pyridines, important chiral building blocks for the preparation of several biologically active compounds, have been synthesized. We have made an attempt to take into account the largest possible number of original papers, including our research and others. Publications of the last eleven years are included in this review.

Keywords: Medium-ring heterocycles, 2,3-dihydro-1,4-benzodioxins, 1,4-dioxino[2,3-b]pyridines, 2,3-dihydro-3-hydroxymethyl-1,4- benzoxazines, 2,3-dihydrospiro-1,4-dioxino[2,3-b]pyridines, Smiles rearrangement, nucleophilic aromatic substitution, novel scaffolds

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Article Details

VOLUME: 15
ISSUE: 6
Year: 2011
Page: [869 - 887]
Pages: 19
DOI: 10.2174/138527211794518925
Price: $58

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