Synthesis of (+)‐trans‐Dihydrolycoricidine by an Organocatalytic Enantioselective Friedel–Crafts Reaction

Abstract

The amaryllidaceae alkaloid (+ +)-trans-dihydrolycoricidine (1)w as synthesized by asymmetric organocatalytic Friedel-Craftsr eaction of sesamol with nitro-olefin followed by an intramolecular Henry reaction for constructiono ft he Cr ing system.C onstructiono ft he Br ing was achieved by am icrowave-assisted palladium-catalyzed CO insertion reaction. Finally,r egio-and stereoselective introductiono ft he third hydroxyl group (at C3) on the Cr ing afforded 1.

Recent Applications of Asymmetric Organocatalytic Methods in Total Synthesis

“…Compound 407 served as the key intermediate for the total synthesis, and further transformations afforded (+)‐ trans ‐dihydrolycoricidine ( 412 ) via a multistep sequence (Scheme 44). [82] …”

“…[81] In 2016, Nagasawa and co-workers reported an enantioselective total synthesis of (+)-trans-dihydrolycoricidine (412, Scheme 44). [82] They first achieved an asymmetric 1,4-Friedel-Crafts reaction between racemic nitroalkene 402 and sesamol (403), using guanidine-bisthiourea 404 as the organocatalyst. The reaction led to the formation of an optically active 405 as an inseparable diastereomeric mixture.…”

Brønsted Acid as Efficient Catalyst for Synthesis of Biologically Active Natural Products

“…In 2015, Nagasawa and co-workers [19] reported an enantioselective Michael addition of a phenol 9 with a nitro-olefin 10 in the presence of guanidine/bisthiourea organocatalyst 11 (Scheme 2). Scheme 2.…”

Recent Advances in Natural Products Synthesis Using Bifunctional Organocatalysts Bearing a Hydrogen‐Bonding Donor Moiety

“…These alkaloids are interesting synthetic targets due to their complex and diverse structures, as well as their biological activities, which include cytotoxicity towards several cancer cell lines . Our group has reported total synthesis of the Amaryllidaceae alkaloid (+)‐ trans ‐dihydrolycoricidine ( 91 ) by applying asymmetric organocatalysis (Scheme ) . For construction of the stereochemistry at C10b, we employed enantioselective 1,4‐Friedel‐Crafts (FC) reaction between sesamol ( 84 ) and nitro olefin 85 in the presence of guanidine‐thiourea bifunctional organocatalyst 83 to obtain the corresponding 1,4‐FC adduct 86 in 93% ee as an inseparable diastereomeric mixture at C2.…”