Synthetic Transformations of Higher Terpenoids. 37. Synthesis and Cytotoxicity of 4-(Oxazol-2-Yl)-18-Norisopimaranes

Abstract

The synthesis and properties of tricyclic diterpenoids containing a C-4 functionalized oxazole ring are reported. The reaction of 4-[5-(bromomethyl)oxazol-2-yl]-18-norisopimarane with sodium azide in the presence of hydrated copper sulfate and sodium ascorbate in DMF gave the corresponding azide, from which new diterpenoid derivatives containing a 1H-substituted 1,2,3-triazol-4-yl substituent were synthesized. Reduction of the azide produced the terpenoid 5-aminomethyloxazole. Reaction of 4-[5-(bromomethyl)oxazol-2-yl]-18-norisopimarane with methyl esters of amino acids in DMF in the presence of potash synthesized compounds with oxazole C-5 amino-acid substituents. Cytotoxicity of the new isopimaric acid derivatives gainst CEM-13, MT-4, U-937, MCF-7, and MDA-MB-231 human tumor cells was studied.