Refernces
10.1016/j.bmcl.2011.05.083
The research focuses on the efficient synthesis of 3-O-thia-cPAs (4a–d), sulfur analogues of cyclic phosphatidic acid (cPA), with the key step being an intramolecular Arbuzov reaction to construct the cyclic thiophosphate moiety. The synthetic route allows for the production of 4a–d in just four steps from commercially available glycidol. Preliminary biological experiments were conducted to assess the inhibitory effect of 4a–d on autotaxin (ATX), an enzyme involved in controlling the concentration of lysophosphatidic acid (LPA), which affects cell proliferation and cancer cell metastasis. The study used various reactants including glycidol, thioacetic acid, methanol, 2,4-dinitrobenzenesulfenyl chloride, and phosphite, among others, to synthesize the target compounds. The chemical structures of the synthesized compounds were confirmed using NMR (1H NMR, 31P NMR, and HH-COSY) and mass spectrometry. The biological activity was evaluated through ATX inhibition assays, which showed that 3-O-thia-cPAs exhibited a similar inhibitory effect on ATX as the original cPA, with the potency order being 2-O-ccPA 3c > 3-O-thia-cPAs 4a–d > cPA 2a.
10.1016/j.tet.2006.12.081
The research aims to design a new biomimetic foldamer that utilizes the weak amine-carbonyl interaction for secondary structure formation, diverging from the conventional reliance on hydrogen bonding. The purpose of this innovative approach is to create soluble oligomers that adopt a defined secondary structure in a given medium, particularly in aqueous environments, which is a challenge for many existing foldamers. The researchers successfully developed an efficient synthesis of a triply protected monomer starting from glycidol, which contains a dioxolane-protected keto group and additional orthogonal protecting groups, namely Fmoc and TBDMS groups. These protecting groups allow for controlled oligomerization similar to Fmoc solid-phase peptide synthesis. The study reports the construction and full characterization of a ketone-protected dimer, trimer, and tetramer, showcasing the potential for this new type of oligomer to form complex structures through weak tertiary amine-carbonyl interactions. The successful synthesis and characterization of these oligomers pave the way for further exploration into their folding patterns and potential applications in bio-inspired materials.
10.1016/S0040-4039(98)01905-4
The research aimed to introduce a fluorine atom into the structure of 3-[2-hydroxy-3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]quinazolin-2,4-(1H, 3H)-dione (4), a compound of interest due to its partial structure similar to previously studied compounds with pharmacological activities. The study explored the reaction of 4 with diethylaminosulfur trifluoride (DAST), expecting a straightforward fluorination. However, instead of the desired product, a 1,2-migration occurred, leading to the formation of N-[2-fluoro-3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]phthalimide (11a) in 13% yield and N-[2-fluoromethyl-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]phthalimide (11b) in 73% yield. The reaction was proposed to proceed through a spiro-aziridinium intermediate, resulting in an unexpected migration. This discovery provides a practical approach for the preparation of 1-fluoroethylamine derivatives and contributes to the understanding of DAST-induced migrations in chemical synthesis. Key chemicals used in the process included DAST, phthalimide, glycidol, 2-methoxyphenylpiperazine, hydrazine monohydrate, isatoic anhydride, and triphosgene.
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