An Efficient Access to 3,5‐Disubstituted Isoxazoles with Anthranilate Ester Moiety: Alkaloid Lappaconitine – Aryl Conjugates with an Isoxazole Linker

• Published in: Asian journal of organic chemistry Vol. 10; no. 10; pp. 2638 - 2643
• Main Authors: Cheremnykh, Kirill P., Savelyev, Victor A., Shults, Elvira E.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01-10-2021
• Subjects: Alkaloids; alkynones; cross-coupling reaction; cyclocondensation; Esters; isoxazoles; Organic chemistry
• ISSN: 2193-5807; 2193-5815
• DOI: 10.1002/ajoc.202100474

Alkynones have gained great attention as useful building blocks in organic synthesis. They have been emerged as key intermediates in the synthesis of various heterocycles. In the present study, the alkynylketones derived from antranylic acids esters or alkaloid lappaconitine were employed as a platform for late‐stage derivatisation. The synthesis of regioisomeric 3,5‐diarylisoxazoles was achieved starting from ethyl N‐acetyl‐5‐iodoanthranilate. A range of 3,5‐disubstituted isoxazoles, containing the plant alkaloid lappaconitine moiety at the C‐3 position were convenience synthesized by a consecutive three‐component alkynylation‐cyclocondensation sequence starting from of 5′‐ethynyllappaconitine, aroyl chlorides, and hydroxylamine hydrochloride. Notably, several 5‐hydroxy‐4,5‐dihydroisoxazoles were obtained in good yields as main products in this three component reaction by using Et3N as the base and i‐PrOH as the solvent in cyclocondensation step.
Alkynylketones, containing an anthranylic acid ester moiety are synthesized and they reactions with nitrogen sourses were studied. A convenient route to hybrid compounds containing alkaloid lappaconitine and aryl fragments connected through an isoxazole ring was developed.