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

Coupling of methyl 16-aminomethyllambertianate with N-Boc-protected ω-amino acids resulted in 16-(N-Boc-aminononan)- and 16-(N-Boc-aminoundecan)amidomethyllabdanoids. Interaction of methyl aminomethyllambertianate with bicyclo[2.2.1]hept-5-en-2,3-dicarboxylic acid anhydride led to the amide of bicyclo[2.2.1]heptan-1,2-dicarboxylic acid with a labdanoid substituent. Reaction of methyl 16-aminomethyllambertianate with chloroacetyl chloride resulted in methyl 16-(chloroacetylaminomethyl)lambertianate; coupling of the latter with methyl esters of amino acids gave the corresponding amides of methyl lambertianate. The compounds obtained were more cytotoxic toward CEM-13, MT-4, and U-937 tumor cell lines as compared with lambertianic acid; the dose inhibiting tumor cell viability by 50% (CCID₅₀) of the more active compounds was 3.9–9.9 μM.