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

Abstract

An almost underexplored field within the natural products area is the synthesis of pseudo‐natural product libraries by employing isocyanide‐based multicomponent reactions as powerful synthetic tools and natural products or their functionalized derivatives as starting reagents. In this work, a novel synthetic strategy behind the late‐stage functionalization of fused Vouacapane‐azoles in a two‐step reaction was developed. The first reaction is a Vilsmeier–Haack formylation at furan ring of the natural product 6β‐acetoxyvouacapane, which was isolated from the leaves of Caesalpinia platyloba from its dichloromethane extracts. The second reaction was a Groebke–Blackburn–Bienaymé reaction to synthesize the pseudo‐natural products 11a‐f in moderate yields, containing pharmacophoric fragments furan and imidazo[1,2‐a]pyridine. The compounds described here are good candidates for biological activity assays.

The Semi-Synthesis of Imidazo-5α-Hydroxyvouacapane from Caesalpinia pulcherrima via a Groebke–Blackburn–Bienaymé Reaction

“…1D-NMR techniques ( 1 H and 13 C) confirmed the presence of the aldehyde proton at δ 9.47 and the carbonyl group at δ 176.8. The yield obtained for this compound was lower than that reported by Servin et al under the same formylation conditions [16]. This variation can be attributed to the fact that the starting material for compound 5 contains a hydroxyl group, which may react with POCl 3 , causing an alcohol dehydration reaction that leads to the formation of alkenes as byproducts.…”

“…Colorless crystals; m.p. 98-100 °C; 1 H-NMR (400 MHz, CDCl3): δ 7.21 (d, J = 1.1 Hz, 1H), 6.18 (d, J = 1.6 Hz, 1H), 2.58 (dd, J = 6.8, 4.1 Hz, 1H), 2.49-2.43 (m, 1H), 2.37-2.35 (m, 1H), In continuation of our studies of natural product derivatives and the synthesis of biologically relevant compounds by using I-MCR such as Ugi-azide and the Groebke-Blackburn-Bienaymé reaction (GBB) [13][14][15][16], herein, we report the isolation of 5α-hydroxyvouacapane 5 and the semi-synthesis of imidazo-5α-hydroxyvouacapane through the GBB reaction.…”

“…Isovouacapenol C 1 [10], pulcherrimin C 2 [11], pulcherrimin A 3 [12], 8,9,11,14-didehydrovouacapen-5α-ol 4, and 5α-hydroxyvouacapane 5 [10] are some of the metabolites isolated in this species, the latter being the natural product under study in this work (Figure 1). In continuation of our studies of natural product derivatives and the synthesis of biologically relevant compounds by using I-MCR such as Ugi-azide and the Groebke-Blackburn-Bienaymé reaction (GBB) [13][14][15][16], herein, we report the isolation of 5α-hydroxyvouacapane 5 and the semi-synthesis of imidazo-5α-hydroxyvouacapane through the GBB reaction.…”