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 Lphenylalanine, 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.

Late‐stage functionalization of Vouacapane derivatives from Caesalpinia platyloba by a Groebke−Blackburn−Bienaymé reaction

“…For instance, isocyanide‐based multicomponent reactions (I‐MCR) have been used for the synthesis of triterpene and marine natural products derivatives, although such reports remain limited. [ 5–9 ]…”

“…[ 7 ] In 2020, Veena et al used coronarin D 6 , which is a labdane diterpene to afford the imidazo[1,2‐ a ]pyridine 8 in 30% yield (Scheme 1B). [ 8 ]…”

“…For instance, isocyanidebased multicomponent reactions (I-MCR) have been used for the synthesis of triterpene and marine natural products derivatives, although such reports remain limited. [5][6][7][8][9] Moreover, the GroebkeÀBlackburnÀBienaymé reaction (GBB) is undoubtedly one of the I-MCR of major biological-synthetic relevances because it allows to obtain N-fused bis-heterocycles such as imidazo [1,2-a]pyridines. Such molecules are considered privileged structures in medicinal chemistry because their derivatives exhibit a plethora of pharmaceutical activities.…”

“…[7] In 2020, Veena et al used coronarin D 6, which is a labdane diterpene to afford the imidazo[1,2-a]pyridine 8 in 30% yield (Scheme 1B). [8] On the other hand, the 6β-acetoxyvouacapane 9 is a tetracyclic diterpene isolated from Caesalpinia platyloba with a fused furan ring in its basic polycyclic skeleton, whose chemical transformations, as well as its stereostructure, have been described by del Rio research group. [16][17][18] To our delight, the 6β-acetoxyvouacapane 9 or their derivatives have not been used as starting reagents in multicomponent reactions.…”

Identification of an Alepterolic Acid Derivative as a Potent Anti‐Breast‐Cancer Agent via Inhibition of the Akt/p70S6K Signaling Pathway

“…Idippily et al synthesized a series of copalic acid (Figure 1) derivatives and found p‐ methoxyphenylamino copalic amide effectively restrained prostate cancer cell growth, possibly by inhibited the chaperone activity of α‐crystallin [33] . Other semi‐synthetic derivatives of labdanes also have been reported [34–38] . However, the anti‐tumor activities and mechanisms of action of alepterolic acid and its derivatives have been rarely reported to date.…”