Functionalization of diazotetronic acid and application in a stereoselective modular synthesis of pulvinone, aspulvinones A–E, G, Q and their analogues

Abstract

A modular synthesis of aspulvinones A, B, C, D, E, G and the recently isolated aspulvinone Q was developed. The methodology features a highly stereoselective aldol condensation of diazotetronic acid with aldehydes to provide 5-arylidene diazotetronates. Subsequent catalytic intermolecular C-H insertion reactions of the arylidene tetronates with arenes provide a series of naturally occurring aspulvinones including aspulvinones C, D and Q which have not been synthesized before. Variation of the aldehyde and the arene components furnishes synthetic analogues of the aspulvinones.

Aspulvins A–H, Aspulvinone Analogues with SARS-CoV-2 Mpro Inhibitory and Anti-inflammatory Activities from an Endophytic Cladosporium sp.

“…The structures of the known compounds ( 9 – 12 ) were determined by comparing their spectroscopic data with the literature values and identified as aspulvinones D, 23 M, 17 O, 22 and R, 16 respectively.…”

“…Also, the 13 C NMR data signals of C-8″ and C-9″ shifted from δ C 70.3 to 91.0 and from δ C 78.7 to 72.5, respectively. These differences in the shifts of the 1 H and 13 C NMR signals indicated the presence of a dihydrofuran in 7 instead of the 25 D −59), indicating that the chiral carbon C-8″ in 7 is consistent with the configuration of aspulvinone F. 17 The structures of the known compounds (9−12) were determined by comparing their spectroscopic data with the literature values and identified as aspulvinones D, 23 M, 17 O, 22 and R, 16 respectively.…”

Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo

“…Butenolides are found in a variety of natural product scaffolds, such as andrographolide [12], aspulvione [13], and uncinine [14]. In addition, butenolides present a series of biologically active properties, including anti-virus, anti-tumor, anti-bacterium, and anti-inflammation [15][16][17].…”

Design and Synthesis of Novel Butenolide Derivatives and Inducing Apoptosis in Gastric Cancer Cells

“…The development of novel therapeutic drugs from medicinal plants has been one of the most important resource to drug development. Natural butenolides, such as aspulvione, [1] uncinine [2] and so on including a similar structures BH3I-1 [3] and obaloclax [4] (Figure 1), have a wide range of biological activities, such as antibacterial, antiviral, anticancer, antimalarial, antibiotic and phospholipase A2 inhibition etc. [5] In connection with previous studies concerning the synthesis and bioactivities of butenolide, [6,7] we are interested in discovery novel anticancer compounds based on the natural product uncinine.…”

“…The combined organic layers were dried over MgSO 4 , concentrated, and purified by silica gel column chromatography [V(acetone)∶V(petroleum ether)＝1∶5] to give 3-(4-(tert-butyl)-benzylidene)-1-(tetrahydro-2H-pyran-4yl)-indolin-2-one (12), 14 mg, yield 44% (yellow oil). 1…”