Synthesis of Tetrahydronaphthalene Lignan Esters by Intramolecular Cyclization of Ethyl p-Azidophenyl-2-phenylalkanoates and Evaluation of the Growth Inhibition of Human Tumor Cell Lines

Abstract

Intramolecular cyclization via nitrenium ion of 2-phenylpentanoic/2-phenylbutanoic acid esters with a terminal p-azidophenyl group gives direct access to tetrahydronaphthalene lignan esters. The p-azidophenyl-substituted butanoate led to an ethyl spirodienone carboxylate, while its homologue pentanoate gave ethyl 4-(4-aminophenyl)-1,2,3,4-tetrahydronaphthalene-1-carboxylate in good yield. In contrast, the m-azidophenyl-substituted esters suffered aromatic nucleophilic addition of trifluoromethanesulfonate. X-ray crystallography established unequivocally the end products structure, and density functional theory studies were performed to rationalize the cyclization outcome. Reaction intermediates and end products were evaluated for their capacity to inhibit in vitro growth of the cell lines MCF-7 (breast cancer), NCI-H460 (lung cancer), SF-268 (CNS cancer), and UACC-62 (melanoma). Growth inhibition of breast, lung, and CNS cancer cell lines was observed with the spirodienone carboxylate, the m-nitrophenylalkyl iodides, and p-phenyl-substituted elongated ethyl esters, namely, the p-nitrophenylpentanoate and p-aminophenylbutanoate, with the latter being also effective on the melanoma cell line.

Stereoselective Synthesis of 5-epi-α-Sialosides Related to the Pseudaminic Acid Glycosides. Reassessment of the Stereoselectivity of the 5-Azido-5-deacetamidosialyl Thioglycosides and Use of Triflate as Nucleophile in the Zbiral Deamination of Sialic Acids

“…This confirms our previous observation using isotopically labelled acetate as nucleophile that doubly substituted products such as 9 are only formed in substrates carrying an axial thioglycoside. 56 …”

“…With regard to the deamination chemistry, we note that the use of levulinic acid as nucleophile in the deamination of the diastereomeric thioglycoside 14 gave 41% of the 5- O -levulinate 16 , via the N -nitroso amide 15 , and that the formation of 4,5-di- O -levulinate diastereomeric with 9 was not observed (Scheme ). This confirms our previous observation using isotopically labeled acetate as nucleophile that doubly substituted products such as 9 are only formed in substrates carrying an axial thioglycoside …”

Synthesis of 2‐(N‐cyclicamino)quinoline combined with methyl (E)‐3‐(2/3/4‐aminophenyl)acrylates as potential antiparasitic agents

“…Compounds 7−13 and 17−22 were synthesized as per reported procedures; physical and spectral properties were in accordance with literature values. [ 33–36 ] The original spectra of the investigated compounds are provided as electronic supporting information (electrospray ionization [ESI]).…”

Rational drug design, synthesis, and biological evaluation of novel chiral tetrahydronaphthalene-fused spirooxindole as MDM2-CDK4 dual inhibitor against glioblastoma

“…After analysing the binding modes of known MDM2 inhibitors and CDK4 inhibitors, we speculated that fusion of the planar tetrahydronaphthalene (THN) ring at the C3-position of oxindole might generate a scaffold that could bind at the P53-binding site in MDM2 as well as at the allosteric site in CDK4. We started with THN 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 and spirooxindole derivatives 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 because they are privileged drug-like architectures, so the resulting THN-fused C3-spirooxindoles should possess good druglikeness ( Fig. 2 C).…”