10.1021/ol0061236
The research aims to achieve the first total synthesis of cristatic acid 1, a secondary metabolite with significant biological properties, including antibiotic activity against Gram-positive bacteria, hemolytic properties, and cytotoxicity. The synthesis is challenging due to the presence of a labile furan moiety, which restricts reaction conditions. The researchers successfully synthesized cristatic acid by employing palladium-catalyzed alkylation of vinylepoxide 10, derived from sulfonium salt 8, and using SEM ethers as protecting groups for phenolic OH functions. Key chemicals used in the process include methyl orsellinate, prenyl bromide, SEMCl, SeO2, tertBuOOH, mesyl chloride, LiBr, Pd(PPh3)4, dppe, and various other reagents for deprotection and functional group transformations. The successful synthesis of cristatic acid not only demonstrates a feasible route to this bioactive compound but also paves the way for further studies on the biological response to changes in functionality. The conclusions of the research confirm the structural integrity of the synthesized cristatic acid through X-ray analysis and other analytical and spectroscopic data, which are in full agreement with literature reports.
10.1016/S0040-4039(00)82268-6
The research focuses on the asymmetric synthesis of α-amino acids, specifically comparing the enolate versus cation functionalization of N-BOC,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-ones (oxazinones 1 and 2). The purpose of this study was to explore the diastereoselectivity of enolate generation and subsequent alkylation of chiral glycinates, as well as the reduction of homologation products to yield Nt-BOC and free α-amino acid derivatives with high enantiomeric excess. The researchers found that using lithium or sodium salts of hexamethyldisilazane in THF at low temperatures effectively deprotonated the substrates without significant decomposition, leading to highly diastereoselective alkylation and the formation of crystalline anti-lactones 3 and 4. The reduction of these lactones resulted in the production of α-amino acid derivatives 5 and 6 with enantiomeric excess exceeding 95%. Key chemicals used in the process included 1-bromo-3-methyl-2-butene, TFA, CH2Cl2, H2, Pd catalyst, and various organometallic reagents. The study concluded that the enolate approach complements electrophilic couplings and expands the versatility of these templates for amino acid synthesis, providing a new method for accessing phenylalanine derivatives and other α-amino acids.
10.1016/S0040-4020(01)96070-3
The research describes the successful total synthesis of the dimeric alkaloid amauromine, a compound of interest due to its unique structure and biological activity as a vasodilator. The purpose of the study was to achieve the first total synthesis of amauromine using a convergent synthetic route based on the thio-Claisen rearrangement reaction through a sulphonium salt, starting from L-tryptophan. Key chemicals used in the synthesis include L-tryptophan, phosphorus pentasulfide, methyl iodide, dicyclohexylcarbodiimide (DCC), N-hydroxysuccinimide (HOSu), potassium carbonate, prenyl bromide, titanium tetrachloride, and lithium aluminium hydride. The synthesis involved multiple steps, including oxidation, esterification, introduction of methylthio function, formation of the key intermediate diketopiperazine, thio-Claisen rearrangement, catalytic reduction, and reductive desulphurization. The final step involved concurrent cyclization and reductive desulphurization using TiCl4-LiAlH4 to obtain amauromine. The study concluded that the total synthesis was achieved with a yield of 15%, and the synthesized amauromine was identical to the natural compound in all respects, confirming the success of the synthetic route. This achievement supports the hypothesis on the mode of introduction of the inverted isoprene unit in related indole alkaloids and provides a potential pathway for the biosynthesis of amauromine.
10.1016/j.bmc.2010.03.015
The research focuses on the synthesis and anti-HIV activity of alkylated quinoline 2,4-diols, based on naturally occurring quinolone alkaloids, buchapine and compound 2. The study aimed to evaluate their potential as anti-HIV agents in human CD4+ T cell line CEM-GFP, infected with HIV1NL4.3 virus. A series of 45 alkylated derivatives were synthesized and tested for anti-HIV potential. The key intermediates, quinoline 2,4-diol and substituted quinoline 2,4-diol, were synthesized through condensation of aniline or substituted aniline with diethyl malonate under microwave irradiation. The synthesis involved various reactants such as prenyl bromide, K2CO3, DMF, and N-methyl 2-pyrolidone (NMP). The biological evaluation included cytotoxicity testing using an MTT-based cell viability assay and anti-HIV activity determination through p24 antigen capture ELISA. The analyses used included nuclear magnetic resonance (NMR), mass spectrometry (MS), infrared (IR) spectroscopy, high-performance liquid chromatography (HPLC), and elemental analysis to confirm the structure and purity of the synthesized compounds. The study identified several potent inhibitors, with compound 6 showing an IC50 value of 2.35 μM and a therapeutic index better than AZT, the standard anti-HIV drug.
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