Dimeric Cinchona alkaloids

Abstract

Nature is full of dimeric alkaloids of various types from many plant families, some of them with interesting biological properties. However, dimeric Cinchona alkaloids were not isolated from any species but were products of designed partial chemical synthesis. Although the Cinchona bark is amongst the sources of oldest efficient medicines, the synthetic dimers found most use in the field of asymmetric synthesis. Prominent examples include the Sharpless dihydroxylation and aminohydroxylation ligands, and dimeric phase transfer catalysts. In this article the syntheses of Cinchona alkaloid dimers and oligomers are reviewed, and their structure and applications are outlined. Various synthetic routes exploit reactivity of the alkaloids at the central 9-hydroxyl group, quinuclidine, and quinoline rings, as well as 3-vinyl group. This availability of reactive sites, in combination with a plethora of linker molecules, contributes to the diversity of the products obtained.

Asymmetric organocatalytic α-amination of 2-oxindoles with bis(2,2,2-trichloroethyl)azo-dicarboxylate

“…7 Instead, at least for 1b the attainment of appreciable ee values with the phthalazine ethers was rather surprising, as 4b affords essentially racemic product in the AαA of the same oxindole substrate with tert-butyl ester 2c. 8 As expected, but not always observed in the organocatalytic applications of dimeric alkaloid derivatives, 16 switching between the pseudo-enantiomeric organocatalyst 4a and 4b (Table 1, entry 6 and entry 5, respectively) caused nearly perfect inversion of the sense of asymmetric induction.…”

Synthesis of Crosslinked Chiral Polysiloxanes of Cinchona Alkaloid Derivatives and their Applications in Asymmetric Catalysis

“…Readily available and inexpensive cinchona alkaloids such as quinine, quinidine, cinchonine and cinchonidine are among the most useful chirality inducers in asymmetric organocatalysis . Despite their stability to moisture and oxygen and being environmentally friendly, cinchona alkaloids possess various functionalities that are available for chemical modifications .…”

Synthesis of C3-Symmetric Cinchona-Based Organocatalysts and Their Applications in Asymmetric Michael and Friedel–Crafts Reactions

“…Cinchona-based C 2 -and C 3 -symmetric compounds have also been widely studied [20]. Jew et al demonstrated the high enantioselectivity of a novel trimeric cinchona alkaloid ammonium salt as a phase-transfer catalyst (PTC) in the catalytic asymmetric alkylation of the N-(diphenylmethylene)glycine tert-butyl ester [21].…”