Shahriar Khadem | PubMed Health

PubMedDate not supplied

A solution- and solid-phase approach to tetrahydroquinoline-derived polycyclics having a 10-membered ring.

With the goal of library generation using a polycyclic derivative 5 having an enamide functional group, a simple and practical, enantioselective synthesis of tetrahydroquinoline derivative 2 was achieved. The phenolic hydroxyl group in compound 2 was utilized as an anchoring site for solid-phase synthesis. The ring closing metathesis approach yielded the desired polycyclic product 5 on solid phase in five steps (overall 40% yield). Compound 5 is a novel scaffold for the library generation of natural product-like polycyclics having a functionalized medium ring for obtaining a new class of small molecules to be utilized as chemical probes.

Journal Article↗

PubMedDate not supplied

Part 1. modular approach to obtaining diverse tetrahydroquinoline-derived polycyclic skeletons for use in high-throughput generation of natural-product-like chemical probes.

A practical synthesis of a tetrahydroaminoquinoline scaffold (12) was developed that used a stereocontrolled aza Michael as the key reaction. Three tetrahydroquinoline alkaloid-like, tricyclic derivatives 16, 18, and 19 with different medium to macrocyclic ring skeletons were obtained, using this scaffold as the starting material, in a modular manner. The macrocyclic compounds with an isolated olefin and an electron-deficient olefin were obtained by ring-closing metathesis approaches. Compounds 16 and 18 are unique and contain bridged 10- and 12-membered functionalized rings. The NMR studies of these compounds revealed interesting information on the conformation of the bicyclic scaffolds that was dependent on the nature and the size of the macrocyclic rings. Finally, this modular methodology, using compound 21 anchored onto the solid support, successfully led to the generation of different macrocyclic derivatives, 23, 25, and 27 in solid-phase synthesis. The solid-phase synthesis approach outlined in this article has the potential to generate tetrahydroquinoline-based tricyclic compounds containing different medium to macrocyclic architectures.

Alkaloids↗