- Synthesis and biological activity of alkynoic acids derivatives against mycobacteria
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2-Alkynoic acids have bactericidal activity against Mycobacterium smegmatis but their activity fall sharply as the length of the carbon chain increased. In this study, derivatives of 2-alkynoic acids were synthesized and tested against fast- and slow-growing mycobacteria. Their activity was first evaluated in M. smegmatis against their parental 2-alkynoic acids, as well as isoniazid, a first-line antituberculosis drug. The introduction of additional unsaturation or heteroatoms into the carbon chain enhanced the antimycobacterial activity of longer chain alkynoic acids (more than 19 carbons long). In contrast, although the modification of the carboxylic group did not improve the antimycobacterial activity, it significantly reduced the toxicity of the compounds against eukaryotic cells. Importantly, 4-(alkylthio)but-2-ynoic acids, had better bactericidal activity than the parental 2-alkynoic acids and on a par with isoniazid against the slow-grower Mycobacterium bovis BCG. These compounds had also low toxicity against eukaryotic cells, suggesting that they could be potential therapeutic agents against other types of topical mycobacterial infections causing skin diseases including Mycobacterium abscessus, Mycobacterium ulcerans, and Mycobacterium leprae. Moreover, they provide a possible scaffold for future drug development.
- Vilchze, Catherine,Leung, Lawrence W.,Bittman, Robert,Jacobs, William R.
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- A novel synthesis of allenes by alkenylation of magnesium alkylidene carbenoids with lithium α-sulfonyl carbanions
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Treatment of magnesium alkylidene carbenoids, which were generated from 1-chlorovinyl p-tolyl sulfoxides with a Grignard reagent by sulfoxide-magnesium exchange, with lithium α-sulfonyl carbanions gave allenes in moderate to good yields. This procedure offers a novel synthetic method for allenes with three-component coupling in relatively short steps.
- Satoh, Tsuyoshi,Sakamoto, Tatsuya,Watanabe, Masanori
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- Synthesis of natural polyacetylenes bearing furan rings
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The first total syntheses of four new polyacetylene compounds have been achieved using convergent routes, which involved Cadiot-Chodkiewicz copper-catalyzed cross-coupling reactions to sp-sp centers as the key steps. 19-Furan-2-ylnonadeca-5,7-diynoic acid (1), 19-furan-2-ylnonadeca-5,7-diynoic acid methyl ester (2), 2-pentacosa-7,9-diynylfuran (3), and 21-furan-2- ylhenicosa-14,16-diyn-1-ol (4) were stable and could be readily identified, isolated, and purified in high overall yields.
- Barancelli, Daniela A.,Mantovani, Anderson C.,Jesse, Cristiano,Nogueira, Cristina W.,Zeni, Gilson
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supporting information; experimental part
p. 857 - 860
(2009/12/26)
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- Reaction of magnesium alkylidene carbenoids with lithium α-sulfonyl carbanions: A novel synthesis of tri- and tetra-substituted allenes from 1-chlorovinyl p-tolyl sulfoxides and sulfones
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Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from ketones and chloromethyl p-tolyl sulfoxide, with ethylmagnesium chloride or isopropylmagnesium chloride at below -78°C gave magnesium alkylidene carbenoids in about 90% yields. The reaction of the generated carbenoids with lithium α-sulfonyl carbanions was found to afford tri- and tetra-substituted allenes. Both cyclic ketones and acyclic ketones were useful in this procedure. However, the 1-chlorovinyl p-tolyl sulfoxides derived from aldehydes gave only rearranged products, acetylenes, under the reaction conditions. The magnesium alkylidene carbenoid derived from an optically active 1-chlorovinyl p-tolyl sulfoxide was treated with lithium α-carbanion of 1-naphthyl phenyl sulfone; however, the obtained allene was found to be racemic. The mechanism of this reaction is also discussed.
- Satoh, Tsuyoshi,Sakamoto, Tatsuya,Watanabe, Masanori,Takano, Koji
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p. 966 - 970
(2007/10/03)
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