Compounds containing the tetrahydroisoquinoline ring system were prepared using solid-supported ester derivatives on a nucleophile-sensitive resin, starting from the corresponding BOC-protected amino acids. The key heterocyclic intermediates were obtained from the Pictet-Spengler reaction between ethyl glyoxylate or methyl 4-formylbenzoate and dopamine or 3-hydroxyphenethylamine. After the resulting amino esters were converted to the BOC derivatives, the phenolic hydroxyl groups were alkylated with a series of alkyl halides to afford the corresponding ethers. Ester hydrolysis afforded the BOC-protected tetrahydroisoquinoline carboxylic acid scaffolds, which were then attached to (4-hydroxyphenyl)sulfide resin (Marshall linker) as the corresponding ester. The BOC group was removed under acidic conditions, and the resulting support-bound amine hydrochlorides were converted to the corresponding amides using a set of carboxylic acids. The support-bound amides were liberated with amines to produce the desired tetrahydroisoquinoline carboxamides. Optimization of the resin loading conditions is described in addition to the identification of impurities observed during the development of the optimum conditions for solid-phase synthesis.
Investigation of Novel Fumagillin Analogues as Angiogenesis Inhibitors. -The synthesis of fumagillin analogue (IX), which shows comparable in vitro and in vivo activity to TNP-470, is described. -(PYUN*, H.-J.; FARDIS, M.; TARIO, J.; YANG, C. Y.; RUCKMAN, J.; HENNINGER, D.; JIN, H.; KIM, C. U.; Bioorg. Med. Chem. Lett. 14 (2004) 1, 91-94; Gilead Sci. Inc., Foster City, CA 94404, USA; Eng.) -M. Schroeter 17-221
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.