Design and synthesis of sinomenine isoxazole derivatives via 1,3-dipolar cycloaddition reaction

Abstract

A novel structure of sinomenine isoxazole derivatives is synthesized from sinomenine hydrochloride and aromatic aldehydes and requires 6 steps. 19 target compounds have been obtained in good yields. The sinomenine hydrochloride transforms to 4-alkynyl sinomenine, which is a key intermediate product to synthesize the target sinomenine isoxazole compounds, after a neutralization reaction with ammonia and substitution reaction with 3-chloropropyne. Another key intermediate product is 1,3-dipole, which can be obtained from aromatic aldehyde. After treatment with hydroxylamine hydrochloride and then sodium carbonate solution, aromatic aldehyde is converted to aldehyde oxime, which reacts with N-chlorosuccinimide (NCS) to afford aryl hydroximino chloride. 1,3-dipole is eventually formed in situ while triethylamine (TEA) in DMF is added dropwise. Then 4-alkynyl sinomenine is added to provide the sinomenine isoxazole derivative via 1,3-dipolar cycloaddition reaction as the key step. All the target compounds are characterized by melting point,

Naturally Occurring Flavonoids and Isoflavonoids and Their Microbial Transformation: A Review

“…Quercetin (63) was produced by an endophytic fungi Psathyrella candolleana from the seed of Ginkgo biloba. It displayed antibacterial activity against S. aureus with MIC values of 0.3906 mg/mL [55].…”

9-Anthraldehyde oxime: a synthetic tool for variable applications

“…The sinomenine free base 21 has been transformed into the 4-alkynyl sinomenine 23, which is the key intermediate for the synthesis of the target compound. The cycloaddition reaction with 9-anthracenenitrile oxide (8a) afforded the sinomenine isoxazole derivative 24 in 79% yield (Scheme 13) [28].…”

The present and future synthetic strategies of structural modifications of sinomenine

“…The tolerance of sinomenine derivative 17 towards 1,3-dipolar cycloadditions was reported. 32 The 1,3-dipole was not prepared from sinomenine due to the incompatibility of the C6-carbonyl group towards its formation. Therefore, the alkyne component was incorporated into the C4-position of 1 by an S N 2 reaction with 3-chloropropyne (Scheme 7).…”