Synthesis of a cytisine/epibatidine hybrid: a radical approach

Minisci reactions: Versatile CH-functionalizations for medicinal chemists

“…The desired cyclized compounds 75 and 76 were tested as racemic mixtures for inhibition of a 4 b 2 nAChRs and showed K i values of 3.5 nM and 0.5 nM respectively. 131 In a further demonstration of intramolecular Minisci reactions to prepare compounds of biological significance, Zard and Gagosz have provided compounds related to the anti-tumor agent PB1 77 (Scheme 46), 132 and Bennesar et al have synthesized the potent anti-malarial/anti-tumor quinone Calothrixin B 78, 133 and ellipticine quinones, such as 79 (Scheme 46), which may also be useful as anti-tumor agents, or as a precursor of ellipticine itself. 134 As mentioned in Section 2.1, radicals can add to heteroaromatic systems that are not basic.…”

Cytisine: a natural product lead for the development of drugs acting at nicotinic acetylcholine receptors

“…33 The synthesis of a cytisine/epibatidine hybrid by Rouden's group can be divided into 2 parts (Scheme 13). 46 Firstly, O'Neill's approach was followed to obtain 85. Then, a radical cyclization was used to produce, after deprotection, 2 compounds (87 and 89) with nanomolar affinity at the a4b2 nAChR subtype.…”

Theoretical prediction on the synthesis of 2,3‐dihydropyridines through Co(III)‐catalysed reaction of unsaturated oximes with alkenes

“…2,3‐Dihydropyridines are not found in bioactive molecules due to their kinetic instabilities. However they are regarded as versatile intermediates in biosynthetic methodology, and can be reduced to piperidines which are important building blocks for numerous pharmaceuticals . Recently, Rovis and coworkers reported the synthesis of 2,3‐dihydropyridines through Cp*Rh(III) complex‐catalysed reaction of unsaturated oximes with alkenes, featuring a broad range of substrates and high diastereoselectivity .…”

“…However they are regarded as versatile intermediates in biosynthetic methodology, and can be reduced to piperidines which are important building blocks for numerous pharmaceuticals. [117][118][119][120] Recently, Rovis and coworkers reported the synthesis of 2,3-dihydropyridines through Cp*Rh(III) complexcatalysed reaction of unsaturated oximes with alkenes, featuring a broad range of substrates and high diastereoselectivity. [121] The actual active species for this reaction is the cationic [Cp*RhOAc] 1 .…”