Total Synthesis of (−)‐Cannabidiol‐C₄

Abstract

Cannabidiol‐C4 1 (CBD‐C4, cannabidibutol) is a natural product that is present in the extracts of Cannabis. Its isolation has not been reported to date. The aim of the proposed synthesis is to secure the availability of the pure compound, its spectroscopic characterization, and to confirm its presence in low amounts in the extracts. The enantioselective total synthesis is based on a) the use 3,5‐dimetoxybenzaldehyde as starting material, b) Corey‐Bakshi‐Shibata reduction, c) Claisen‐Ireland rearrangement, d) ring‐closing metathesis, and e) completely not‐trivial demethylation induced by sodium ethanethiolate.

Piers–Rubinsztajn reaction to unlock an 8-step synthesis of 7-hydroxy cannabidiol

“…While we were facing this challenge, Passarella and co-workers reported the successful deprotection on small scale of dimethoxy CBD 3 to CBD 2 by using a large excess of NaSEt, in two sequential steps, isolating the monodeprotected intermediate. 19 Unfortunately, the same protocol did not prove successful in our hands for the deprotection of dimethoxy derivative 6; 7-OH CBD 1 was obtained in very low yield and only detectable by mass spectrometry. Derivatization of phenolate 7 with an easily removable electron-withdrawing group to affect the second deprotection was attempted, along with adjusting the pH, to no avail.…”

Total Synthesis and Biological Activity of (±)-Guignardin A, (±)-Palmarumycin B9, and Their Derivatives

“…Compound 1g was decomposed (Table S7, entries 1–3), so as compound 1d (Table S7, entries 4 and 5). Fortunately, compound 1h was successfully prepared in 96% yield when NaSEt was used as an appropriate demethylation reagent in this reaction − (Scheme ). After the Davis oxidation of 1h and Wacker oxidation of 1i in sequence, the first total synthesis of (±)-guignardin A ( 1 ) was completed in 14.9% overall yield in seven steps from 5-methoxy-1-tetralone 1a .…”

Total Synthesis of Kuwanons A and B and Discovery of Their Antibacterial Mechanism

“…We then attempted to use a nucleophilic reagent for the debenzylation. Although the existing methods for deprotection with nucleophilic reagents were implemented with EtSH, n -BuLi, and hexamethylphosphoric triamide (HMPA), , we decided to abandon this system due to the penetrating odor of EtSH. Alkanethiols with a chain longer than 12 carbons are considered odorless, so we attempted to use 1-dodecanethiol and a suitable base, such as NaOH, NaOMe, or NaH, to obtain the highly nucleophilic dodecane-1-thiolate (RS – , Scheme ) to debenzylate 16 .…”