Gold(I)-Catalyzed Synthesis of 4H-Benzo[d][1,3]oxazines and Biological Evaluation of Activity in Breast Cancer Cells

Abstract

The first gold(I)-catalyzed cycloisomerization procedure applied to the synthesis of substituted 4 H -benzo[ d ][1,3]oxazines has been developed starting from N -(2-alkynyl)aryl benzamides. The chemoselective oxygen cyclization via the 6- exo -dig pathway yielded the observed heterocycles in modest to good chemical yields under very mild reaction conditions. The obtained oxazines were assayed on the breast cancer (BC)-derived cell lines MCF-7 and HCC1954 with differential biological activity. The newly synthesized 4 H -benzo[ d ][1,3]oxazine compounds showed several degrees of cell proliferation inhibition with a remarkable effect for those compounds having a substituted aryl at C-2 of the molecules. The 4 H -benzo[ d ][1,3]oxazines showed an IC 50 ranking from 3.1 to 95 μM in MCF-7 and HCC1954 cells. These compounds represent potential drug candidates for BC treatment. However, additional assays are needed to elucidate their complete effect over the cellular and molecular hallmarks of cancer.

Divergent Sequential Reactions of β‐(2‐Aminophenyl)‐α,β‐ynones with Malonyl Chloride

“…The gold(I)‐catalyzed cycloisomerization of 3 ab achieved the isolation of the corresponding ( Z )‐1‐phenyl‐2‐(2‐phenyl‐ 4H ‐benzo[ d ][1,3]‐oxazin‐4‐ylidene)ethan‐1‐one 5 ab in high yield (Scheme 4). [28] This represent the first application to the synthesis of benzo[d][1,3]oxazines from β‐(2‐aminophenyl) α,β‐ynones 1 . The diversity oriented synthesis of new benzo[ d ][1,3]oxazines is of great relevance because their applications in the field of development of effective pharmaceuticals and electronic materials [28,29] .…”

“… [28] This represent the first application to the synthesis of benzo[d][1,3]oxazines from β‐(2‐aminophenyl) α,β‐ynones 1 . The diversity oriented synthesis of new benzo[ d ][1,3]oxazines is of great relevance because their applications in the field of development of effective pharmaceuticals and electronic materials [28,29] . On the other hand, as stated above, 6 ab derivative should be easily obtained from 5 ab by hydrolysis.…”

Synthesis andin vivoEvaluation of Fluorobenzyl Metformin Derivatives as Potential Drugs in The Diabetes Treatment

“…Organic chemistry is, among the scientific disciplines, the most used tool to obtain treatments for clinical and/or biological affections. This discipline has been evolving with time, increasing the development of compounds with high pharmaceutical interest, using strategies such as metal-catalyzed, [1,2] metalfree [3][4][5][6][7][8][9][10] or natural occurring compounds synthesis and derivatization. [11][12][13] These compounds have been developed with specific goals, such as for the treatment of cancer, [14,15] mycoses, [16] polycystic ovarian, pain, inflammation [17] hyper-glycemia and lastly but not less important: diabetes mellitus.…”

Catalyst-Free Synthesis of Functionalized 4-Substituted-4H-Benzo[d][1,3]oxazines via Intramolecular Cyclization of ortho-Amide-N-tosylhydrazones

“…Given the wide biological applications of 4 H -benzo­[ d ]­[1,3]­oxazines, synthetic strategies to prepare these molecules have gained considerable interest among organic chemists over the past decades …”