Semi-synthetic diversification of coronarin D, a labdane diterpene, under Ugi reaction conditions

Abstract

The prevalence of 5-hydroxydihydrofuran-2(3H)-one moiety in natural products is exploited for the first time using coronarin D, a labdane diterpene, to afford Ugi reaction product 1a and interrupted Ugi product 2a. The potential of the Ugi reaction was further extended to l-phenylalanine, 2-aminopyridine, and d-glucosamine, which afforded Ugi reaction products 3a–f, 4, and 5a–d, respectively. Cytotoxicity studies in RAW cells reveal that compounds 3e and 5b were non-toxic up to 50 µM, and these compounds were able to reduce the LPS stimulated NO production in RAW cells in par with the standard anti-inflammatory drug dexamethasone.

Graphical Abstract

Keywords:

• Semi-synthesis
• multicomponent reaction
• Ugi reaction
• labdane diterpene
• 5-hydroxydihydrofuran-2(3H)-one
• coronarin D

Disclosure statement

There are no conflicts of interest to declare.

Additional information

Funding

Financial support from Department of Science and Technology (DST), India, grant no. CRD/2018/000064 is gratefully acknowledged.