Synthetic transformations of higher terpenoids. XXVI. 16-acetylaminomethyllabdanoids and their cytotoxicity

Abstract

Condensation of methyl 16-aminomethyllambertianate with N-Boc-omega-amino acids leads smoothly to 16-(N-Boc-aminononan)- and 16-(N-Boc-aminoundecan)amidomethyllabdanoids. The amide of bicyclo[2.2.1]heptan-1,2-dicarbocylic acid with a labdanoid substituent was obtained under the reaction of methyl aminomethyllambertianate with bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride. Intereaction of methyl 16-aminomethyllambertianate with chloroacetyl chloride leads to methyl 16-(chloroacetylaminomethyl)lambertianate; condensation of this compound with amino acid methyl ethers the corresponding amides of methyl lambertianate was obtained. The resulting compounds are more (compared with lambertianic acid) cytotoxicity in the cell lines CEM-13, MT-4 and U-937 with an CCID50 concentration of 3.9-9.9 microM.

Synthetic transformations of higher terpenoids: XXVIII. Diels-Alder reactions of 16-(trimethylsiloxybutadienyl) labdanoids

“…We previously reported on modification of the furan ring in I and II, which afforded pharmacologically important compounds exhibiting analgesic activity [5] and cytotoxicity against CEM-13, MT-4, and U-937 model tumor cells [6]; they also turned out to regulate cytostatic polychemotherapy [7]. In the present article we describe the synthesis of furanolabdanoid derivatives having an additional pharmacophoric fragment (naphthoquinone or isoindoledione) on C 16 .…”