Enantioselective Total Synthesis of Cannabinoids via a Tandem Conjugate Addition/Enolate Alkylation Annulation with Ambiphilic Organoboronates

Abstract

Cannabinoid research depends on synthesizing derivatives for structure−activity relationship studies. (−)-Δ 9 -Tetrahydrocannabinol and cannabidiol were synthesized via a tandem enantioselective conjugate addition/enolate alkylation annulation with a novel ambiphilic trifluoroborate in seven steps. A new class of alkenyl and aryl ambiphilic trifluoroborates were synthesized and showed great compatibility with various functional groups, high yields, and excellent enantio-and diastereoselectivity. A novel benzo-fused cannabinoid analogue and tandem quaternary stereocenter-containing reaction products were synthesized with good to excellent enantioselectivity. S ince the discovery of (−)-Δ 9 -tetrahydrocannabinol (THC) in 1964 [1 (Figure 1)], 1 chemists have been attracted to

Therapeutic Potential of Minor Cannabinoids in Dermatological Diseases—A Synthetic Review

“…Chemical synthesis is a process that involves transforming available chemical precursors into desired cannabinoid molecules through chemical reactions such as condensation, acylation or reduction. Chemical synthesis offers a wide range of possibilities for structural modifications, which can lead to cannabinoids with increased activity, selectivity, or stability [ 6 ]. The condensation method is used to create cannabinoids through chemical reactions between precursors, forming the cannabinoid ring structure.…”

Asymmetric Synthesis of (−)-Cannabidiol (CBD), (−)-Δ9-Tetrahydrocannabinol (Δ9-THC) and Their cis Analogs Using an Enantioselective Organocatalyzed Diels–Alder Reaction

“…Kobayashi introduced the chirality of the terpenic moiety via enzymatic hydrolysis of cis -1,4-diacetoxycyclohexane (Figure A, i) . Grimm reported an enantioselective carbonyl-ene reaction with neral (Figure A, ii), and simultaneously, Luo and May used an annulation reaction that provided key intermediates for the synthesis of CBD with high enantioselectivity (Figure A, iii) . Shultz opted to use a functionalized olivetol derivative that was reduced either catalytically using Corey’s chiral oxazaborolidine (CBS) or enzymatically (Figure A, iv).…”

“…6 Grimm reported 7 an enantioselective carbonyl-ene reaction with neral (Figure 1A, ii), and simultaneously, Luo and May used an annulation reaction that provided key intermediates for the synthesis of CBD with high enantioselectivity (Figure 1A, iii). 8 Shultz opted to use a functionalized olivetol derivative that was reduced either catalytically using Corey's chiral oxazaborolidine (CBS) or enzymatically (Figure 1A, iv). In this case, the enzymatic process provided higher enantioselectivity.…”