Azepino- and Diazepinoindoles: Synthesis and Dopamine Receptor Binding Profiles

Stereocomplementary Chemoenzymatic Pictet–Spengler Reactions for Formation of Rare Azepino-indole Frameworks: Discovery of Antimalarial Compounds

“…Previously reported seven-membered azepino and diazepino-indoles exhibited dopamine receptor binding activity on bovine D1 and human D2 receptors . These indolic compounds were, however, non-chiral in contrast to our azepino-indoles with ( R )- and ( S )-configuration at carbon 4 depending on the method applied: Enzyme catalysis by STR1 results in formation of 4α-( S ), KPi-dependent leading to a 4β-( R ) configuration. Phosphate-dependent biomimetic synthesis of tetra-hydroisoquinoline alkaloids was reported to be achieved through either asymmetric or symmetric PSRs, in which a complementary stereoselective synthesis by norcoclaurine synthase and phosphate buffer was realized by Eddmann et al Our herein chemical route in KPi buffer might suggest a similar reaction mechanism.…”

“…Previously reported seven-membered azepino and diazepino-indoles exhibited dopamine receptor binding activity on bovine D1 and human D2 receptors . These indolic compounds were, however, non-chiral in contrast to our azepino-indoles with ( R )- and ( S )-configuration at carbon 4 depending on the method applied: Enzyme catalysis by STR1 results in formation of 4α-( S ), KPi-dependent leading to a 4β-( R ) configuration.…”

New Trends and Future Opportunities in the Enzymatic Formation of C−C, C−N, and C−O bonds

“…[169] Molecules containing the azepino [3,4,5-cd] indole core have displayed dopamine receptor binding activity, showing potential as drugs for neuropsychiatric diseases. [170] The group reported the PS reaction between tryptamine analogue 1H-indole-4-ethanamine and secologanin catalysed by STR1 to furnish a tricyclic intermediate with > 98 % de, which was subsequently cyclised to afford the corresponding lactam in 24 % isolated yield (Scheme 19). The lactam was then converted in four steps to the azepino [3,4,5-cd] indole with an overall yield of 26 %.…”

Stereodivergent synthesis of enantioenriched azepino[3,4,5-cd]-indoles via cooperative Cu/Ir-catalyzed asymmetric allylic alkylation and intramolecular Friedel–Crafts reaction

“…We anticipated that the ambiphilic π-allyl-iridium species in situ generated from 4-indolyl allylic carbonates may serve as a unique 4-atom unit in formal 1,3-dipolar (3 + 4) cycloaddition of azomethine ylides, 15 providing a novel route to azepino[3,4,5- cd ] indole derivatives through asymmetric allylic alkylation 16 followed by intramolecular Friedel–Crafts reaction 17 (Scheme 1b). The chiral azepino[3,4,5- cd ] indole framework is present in numerous bioactive compounds and pharmaceuticals, 18,19 while very few examples have been documented for its enantioselective preparation so far. 20 Herein, we report the development of cooperative Cu/Ir-catalyzed formal 1,3-dipolar (3 + 4) cycloaddition of azomethine ylides to afford azepino[3,4,5- cd ]-indole derivatives bearing three stereogenic centers with high diastereo- and enantiocontrol.…”