Quinoline linker

Beyond those often-used hnkage strategies, some more seldom carboxyhc acid-forming variations should be mentioned. A quinoline linker system cleavable via two mild reactions was developed for peptide synthesis in 1999. 

Instead, evidence now favors the intermediacy of the highly organized mono-osmium complex 15. Various factors could contribute to its excellent enantioselectivity, the most important one being the formation of a binding site consisting of the two methoxy quinolines and the pyridazine linker. As confirmed by X-ray analysis and NMR studies [35,36], this pocket adopts a U-shaped conformation and is capable of perfectly binding aromatic substrates such as styrene through attractive interactions with the methoxyquinolines. In contrast, bulky... 

In addition to analogs incorporating an olefinic double bond as a linker between the macrolactone ring and different types of heterocycles, we have also studied a new family of side-chain modified structures, which are characterized by rigidifica-tion of the entire side-chain manifold (exemplified for quinoline-based analogs 30 and 31). ... 

Quinoline-type Cinchona alkaloids (1-4) ccmsist of an aromatic quinoline (or 6 -methoxyquinoline) ring joined to the bulky bicyclic quinuclidine moiety by a carbinol linker C-9. Each Cinchona alkaloid contains five stereogenic centers at C-9, C-8, C-4, C-3, and N-1 (Fig. 21.2). 

Several derivatives of quinoline scaffold with a flexible, semi-flexible or rigid side chains at position 8 of the quinoline ring were synthesized by Arafa et al. [25], Studied in-vitro activity versus the human colon cancer cell line HT29 and the human breast cancer cell line MDA-MB231. The derivatives with Schiff s base linkers showed excellent activity. 

The approach of Wang et al. [78] uses the redox-sensitive nature of quinoline structures that form dihydro quinolines in the presence of mild reducing agents and cyclize after treatment with TEAR Another special linker type is the class of allylic linkers because they can be cleaved by Pd-catalysis via allyl transfer to give carboxylic acids [79]. 

Many modulations of the trioxaquine structure are possible (quinoline, diene, linker), and a number of them have been made, leading to a large femily of new antimalarial compounds that are now under biological investigation. 

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