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

被引：2
|
作者：
Pauvert, Yann [1 ]
Charette, Andre B. [1 ]
机构：
[1] Univ Montreal, Ctr Continuous Flow Synth, Dept Chim, FRQNT Ctr Green Chem & Catalysis, Montreal, PQ H2V 0B3, Canada
来源：
ORGANIC LETTERS | 2024年 / 26卷 / 29期
基金：
加拿大自然科学与工程研究理事会; 加拿大创新基金会;
关键词：
MICHAEL REACTION; CANNABINOIDS; ALDEHYDES;
D O I：
10.1021/acs.orglett.4c01622
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Herein we describe an asymmetric synthesis of the pharmacologically relevant natural (-)-trans-CBD and psychoactive (-)-trans-Delta(9)-THC, as well as their synthetic cis diastereomers. The key step is an enantioselective Diels-Alder reaction catalyzed by a prolinol-based catalyst, which provides the cyclohexene carbaldehyde intermediate in good yield and high enantiomeric excess. Optimization of the substituted resorcinol protecting groups to avoid harsh and low-yield deprotection of the acid sensitive resorcinol moiety is also described.
引用
收藏
页码：6081 / 6085
页数：5
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