A novel approach to 2-arylmethyl-2,3-dihydro-4(1H)-quinazolinones. Total synthesis of the alkaloids glycozolone-A and glycozolone-B

Abstract

2-Arylmethyl-2,3-dihydro-4(1H)-quinazolinones are a small subgroup of the class of quinazolin-4-one alkaloids, and most published total syntheses require the use of unstable and poorly accessible arylacetaldehydes. Here we show that easily available, stable ω-methoxystyrenes are versatile substitutes for arylacetaldehydes. This new methodology was applied to the total synthesis of the alkaloids glycozolone-A and glycozolone-B. The limitations of this new approach were analyzed as well. In this course, new total syntheses of two 2-arylmethyl-4(1H)-quinazolinone alkaloids (glycosminine, 2-(4-hydroxybenzyl)-4(1H)-quinazolinone) were developed as well.

Graphical Abstract

Keywords:

• Alkaloid
• quinazolinones
• total synthesis
• arylacetaldehydes
• cyclization

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

See Supplementary material for experimental details including analytical data and copies of ¹H- and ¹³C-NMR spectra of the synthesized alkaloids.

Additional information

Funding

This work was supported by the German Bundesagentur für Sprunginnovationen (SPRIN-D; Challenge ‘Ein Quantensprung für neue antivirale Mittel’). The authors thank Dr. Lars Allmendinger for support in the interpretation of NMR spectra.