Abstract:A broad biological screening of the natural alkaloid N-methylisosalsoline (2) extracted from Hammada scoparia leaves against a panel of human and parasitic proteases revealed an interesting activity profile of 2 towards human 20S proteasome. This outcome suggests that the 1,2,3,4-tetrahydroisoquinoline skeleton may be exploited as a template for the development of novel anticancer agents. In this article, we report the synthesis and chemical characterization of a new series of isosalsoline-type alkaloids (10-11) with variations at N2 and C3 positions with respect to the natural Compound 2, obtained by a synthetic strategy that involves the Bischler-Napieralski cyclization. The substrate for the condensation to the tetrahydroisoquinoline system, i.e., a functionalized β-arylethyl amine, was obtained through an
OPEN ACCESSMolecules 2015, 20 14903 original double reduction of nitroalkene. The synthetic strategy can be directed to the construction of highly substituted and functionalized 1,2,3,4-tetrahydroisoquinolines.
Cohalogenation by N-bromosuccinimide in methanol of (S-bromoallenyl ethers (3a-g) or ally1 allenyl ethers (8d-f) affords unsaturated halogeno-compounds (5a-g) or (9d-f) which are converted via homolytic carbocyclization into a-methylene-y-butyrolactones (7a-g).
Allenyl Allylic Ethers: Synthesis and Thermal Rearrangements.-Thermal isomerization of the allenyl allylic ethers (I), (III), (V) or (VII) leads either to the products (II) of Claisen rearrangement or by alternate modes of (2 + 2) cycloaddition involving biradical intermediates to the polycyclic structures (IV), (VI) or (VIII). The variations in these reactions are mainly a function of ring size. -(DULCERE, J.-P.; CRANDALL, J.; FAURE, R.; SANTELLI, M.; AGATI, V.; MIHOUBI, M. N.; J.
Allenyl Ethers as Precursors of α-Methylene-γ-butyrolactones and Botryodiplodin Derivatives.-The alkenes (I) are converted into the β-bromopropargyl ethers ( III), which undergo isomerization into the allenyl derivatives (IV). Application of the sequence cohalogenation/isomerization/ dehydrohalogenation to (IV) gives the propargyl acetals (VI), which are precursors of the methylenebutyrolactones (VII). The application of this procedure to the synthesis of the mycotoxin botryodiplodin (XI) is reported, but rapid decomposition makes the isolation impossible. -(DULCERE, J.-P.; MIHOUBI, M. N.; RODRIGUEZ, J.; J.
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