Total Synthesis of (+)-Hinckdentine A: Harnessing Noncovalent Interactions for Organocatalytic Bromination

Abstract

Hinckdentine A, a marine-sponge-derived tribrominated indole alkaloid bearing a unique indolo[1,2- c ]quinazoline skeleton, was completed in 12 steps featuring the construction of the Nα-quaternary carbon center by asymmetric azo-ene cyclization. A novel organocatalyst was developed to promote high-yielding tribromination, which represents a challenging process encountered in previous syntheses. Density functional theory calculations scrutinized viable substrates and deciphered the origin of the enhancement of C8 electrophilic bromination with a bifunctional organocatalyst. Moreover, the application of organocatalyst-enabled bromination on various substrates was demonstrated to highlight future late functionalizations of biologically intriguing targets.

Madangamine alkaloids: Madness and tranquility

“…To simulate natural blueprints, the biogenetic hypothesis should be followed as strategic guidance instead of stringent instruction. [43,44,45] Any adjustment would be necessary to realize the key transformation and preclude side pathways. A compromised narrative ratified in the sensation of biomimetic synthesis was that practical considerations become secondary to theoretical success if the isolated yield is extremely low.…”

Enantioselective total syntheses of (−)-cephalotaxine and (−)-amathaspiramide F through a key Ir/Cu dual catalysis

“…7 Hinckdentine A 8 ( 5 ), another bromo-substituted marine alkaloid, despite lacking biological activities due to its natural scarcity, has been an ideal target for developing synthetic strategies for total synthesis in recent years. 9 Sessilistemonamine A ( 6 ), a sub-family of Stemona alkaloids, poses a significant challenge to synthetic chemists due to its complex structure. 10 Intrigued by the biological activity and particularly the stereochemical complexity found within cephalotaxine and amathaspiramide F, we endeavoured to achieve their asymmetric total syntheses through a unified and yet-to-be-explored strategy.…”

In-water oxidative Suzuki coupling of arenes and arylboronic acids using H2O2 as a terminal oxidant

“…Finally, we showcased the practical utility of our oxidative coupling by arylation of drug molecules. Two approved drug molecules: gemfibrozil and xanthotoxin, 48 were arylated with arylboronic acids under the optimal conditions to provide their derivatives ( 3ac–3af ) in good to excellent yields. These positive results suggest that our oxidative coupling was compatible with various functional groups, including carboxylic acids, esters, and furans.…”