Synthetic studies towards the mulberry Diels–Alder adducts: H-bond accelerated cycloadditions of chalcones

Abstract

The methyl ether derivatives 2, 4 and 6 of the mulberry Diels-Alder adducts chalcomoracin (1) and mulberrofuran C (3) and kuwanon J (5) respectively have been synthesized by a thermal [4 + 2]-cycloaddition reaction between a chalcone and dehydroprenyl diene. A H-bonded ortho OH substituent on the chalcone was found to be essential for Diels-Alder reactivity. Density functional theory calculations show that the OH group lowers the barrier for the Diels-Alder reaction by 2-3 kcal mol(-1) compared with OMe. The acceleration by the OH group is traced to two transition-state effects: a stronger diene-chalcone interaction and better planarity of the aryl-diene unit.

Model studies on construction of the oxabicyclic [3.3.1] core of the mulberry Diels–Alder adducts morusalbanol A and 441772-64-1

“…The same reaction between diene 1b and dienophile 2b also gave the desired cycloadducts in 49% yield as an inseparable 1:1 mixture of endo/exo diastereomers (3b and 4b, Table 1, entry 2). Following Rizzacasa and co-workers' report of the substantial rate enhancement for the Diels-Alder reaction for a hydrogen-bonded ortho OH substituent on a chalcone dienophile, 8 we also examined the thermal Diels-Alder reaction of diene 1a with dienophiles 2c and 2d, both of which lacked an ortho OH substituent. As expected, all attempts to perform the thermal Diels-Alder reaction between diene 1a and dienophiles 2c or 2d failed to yield the desired products (Table 1, entries 3 and 4).…”

Biosynthesis and Biomimetic Synthesis of Flavonoid Diels-Alder Natural Products

“…In their pioneering studies, the callus tissues induced from the leaves or seedlings were cultivated and subjected to selection over a period of 9 years for cell strains with high-pigment productivity [14]. Extraction of these high pigmented cell cultures resulted in isolation of six Diels-Alder adducts, kuwanons J (1), Q (23), R (24), V (25), mulberrofuran E (26), and chalcomoracin (27) along with morachalcone A (28), isobavachalcone (29), and moracin C (30) (Figure 3) [15][16][17][18].…”

“…During the early studies of the Diels-Alder cycloaddition reaction, the reaction was essentially carried out under thermal conditions owing to the simplicity of the experimental setup Flavonoids -From Biosynthesis to Human Health and the efficiency of the thermal process. Today, thermal promoted Diels-Alder cycloaddition reaction remains the first line approach for the construction of a six-membered cyclic compound, including that of flavonoid Diels-Alder natural products [24][25][26][27][28][29][30].…”

“…They hypothesized that the presence of an ortho-phenol group in the chalcone dienophile was essential for the Diels-Alder cycloaddition reaction. However, attempts to deprotect the methyl ethers of these Diels-Alder adducts using various demethylating agents were unsuccessful [25].…”

Progress on the Asymmetric Diels-Alder Reaction ofα,β-Unsaturated Carbonyl Compounds

“…目前仅有加热 [62] 、单电子转移 [63] 和纳米银 颗粒 [64] 三种方法可以促进[4＋2]环合反应, 但是这三种 催化体系的底物适用范围窄, 只能合成一种或少数几种 天然产物或者天然产物类似物, 而且合成得到的都是消 旋化合物. 因此, 不对称全合成该类天然产物成为国内 外化学家的热点研究课题 [65] .…”