10.1016/j.tetasy.2008.01.031
The research focuses on the chemoenzymatic preparation of enantiopure LL-benzofuranyl- and LL-benzo[b]thiophenyl alanines, which are important components in biological and pharmaceutical products. The study combines lipase-mediated dynamic kinetic resolution (DKR) with chemical and enzymatic hydrolytic steps to synthesize the enantiopure amino acids. The experiments involve the use of various commercially available starting materials, such as benzofuran, benzo[b]thiophene, and 1-(2-hydroxyphenyl)ethanone, which are transformed through a series of chemical reactions, including formylation, chloromethylation, and cyclisation, to produce the desired aldehydes and subsequently the racemic amino acids and their derivatives. The enzymatic DKR is then carried out using Novozyme 435 in different alcohols and solvents to achieve high enantioselectivity. The stereoselectivity and conditions of DKR are investigated, and the enantiomeric excess (ee) is determined using HPLC analyses with chiral columns. The research also includes the use of Acylase I for the kinetic resolution of racemic 2-acetamido-3-(heteroaryl)propanoic acids, leading to the final enantiopure products. The analyses used in this study include NMR spectroscopy, mass spectrometry, HPLC, and specific rotation measurements to confirm the configuration and purity of the synthesized amino acids.
10.1021/acs.orglett.5b00523
The study presents a novel domino annulation strategy for the synthesis of benzo[b]thiophenes, which are important heterocyclic compounds found in bioactive natural products and used in medicinal and material chemistry. The researchers used α-alkenoyl-α-alkynyl ketene dithioacetals and cyanoacetates as starting materials, along with Cs2CO3 and Ag2CO3 as catalysts, in a reaction carried out in CH3CN at 110 °C under nitrogen. This approach efficiently yields multisubstituted benzo[b]thiophenes through a tandem thien- and benzannulation process. The purpose of these chemicals was to construct both benzene and thiophene rings in a single pot, providing a new and efficient method for synthesizing benzo[b]thiophenes with potential applications in the pharmaceutical industry and material science.
10.1021/acs.joc.0c01516
The study focuses on the synthesis of 2,5-disubstituted thiophenes and 2-substituted benzo[b]thiophenes using the trithiocarbonate anion (CS32-) as a sulfur source. This anion was generated in situ from carbon disulfide (CS2) and potassium hydroxide (KOH) in dimethyl sulfoxide (DMSO). The purpose of these chemicals is to serve as a novel synthetic equivalent of the S2- synthon, which is used for the cyclization of 1,3-butadiynes and 2-haloalkynyl (hetero)arenes. The study aims to provide a cheap and readily available method for the synthesis of these compounds, which have applications in various fields such as biochemistry, materials chemistry, and organic synthesis. The use of CS32- allows for metal-free cyclization reactions, offering a moderate to good yield of the target compounds with good functional group tolerance.
10.1016/j.bmc.2011.07.056
The research focuses on the design and synthesis of 1,3-biarylsulfanyl derivatives as potential new anti-breast cancer agents. The purpose of this study was to develop novel estrogen receptor ligands by modifying the benzothiophene core of raloxifene, a known selective estrogen receptor modulator (SERM), to create secoraloxifene scaffolds. The synthesized compounds were screened for their anti-proliferative, anti-osteoporotic, and anti-implantation activities. The research concluded that certain compounds, particularly those with basic amino anti-estrogenic side chains (35, 36), showed significant anti-proliferative activity in various cancer cell lines and also exhibited anti-osteoporotic activity comparable to raloxifene. The chemicals used in the synthesis process included substituted chalcones, mercaptans, zirconium chloride as a catalyst, and various alkyl thiols and alkylamines for the introduction of the antiestrogenic side chain. The study suggests that these 1,3-biarylsulfanyl derivatives could be potential candidates for the treatment of breast cancer and osteoporosis.
10.1021/jo00295a038
The research focuses on the synthesis and chemical reactions of thieno[2,3-c]pyrroles. The authors developed a novel method for synthesizing these compounds through a retro-malonate addition reaction, starting from 3-methyl-2-thiophenecarboxaldehyde and diethyl malonate. They also explored the Diels-Alder reactions of thieno[2,3-c]pyrroles with reactive dienophiles such as N-phenylmaleimide and dimethyl acetylenedicarboxylate, leading to the formation of cycloadducts. The study includes the synthesis of various N-substituted thieno[2,3-c]pyrroles and their subsequent reactions to produce compounds like benzo[b]thiophene. The research also investigates the free-energy barriers of inversion of the imine nitrogens in the cycloadducts using variable-temperature 'H NMR spectroscopy. The study provides valuable insights into the synthetic utility and reactivity of thieno[2,3-c]pyrroles, contributing to the field of organic chemistry and potentially to the development of new pharmaceuticals and electroconducting polymers.
10.1021/acsmedchemlett.0c00588
The study explores modifications to the indole-2-carboxamide scaffold to improve the solubility and potency of mycobactericidal agents against Mycobacterium tuberculosis (M. tb). The researchers found that replacing the carboxamide linker with a protonatable aminomethyl side chain, and substituting the indole ring with benzothiophene or benzoselenophene, led to significant improvements in solubility (10-20-fold) without compromising potency. The indolylmethylamine compound 33 (N-cyclooctyl-6-trifluoromethylindol-2ylmethylamine) emerged as a promising candidate with a MIC90 of 0.13 μM against M. tb and MBC99.9 of 0.63 μM, showing comparable activity to its carboxamide equivalent. This compound also inhibited the mycolate transporter MmpL3, a key target for several indolecarboxamides. The study highlights the potential of these structural modifications to enhance the therapeutic potential of indole-based mycobactericidal agents.
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