Total Synthesis of the Naturally Occurring Glycosylflavone Aciculatin

Abstract

The new flavone-glycoside aciculatin (1), from Chrysopogon aciculatus, has been shown to have cytotoxic, anti-inflammatory, and antiarthritis activity. Further biological studies have been limited because of the limited availability of 1 from natural sources. Herein the first total synthesis of 1 in an overall yield of 8.3% is described. The synthesis involved the regio- and stereoselective glycosylation-Fries-type O-to-C rearrangement to construct the C-aryl glycosidic linkage, followed by a Baker-Venkataraman rearrangement and cyclodehydration to form the flavone scaffold.

Total Synthesis of Aryl C-Glycoside Natural Products: Strategies and Tactics

“…As long as the glycosyl donor A is sufficiently activated by Lewis acids or other reaction promoters, this facile process proceeds even at −78 °C (typically employed in the initial studies). Thus, various glycosyl donors, including glycosyl fluorides as above, ,,,− and glycosyl acetates, ,,,− 1-OH sugars, − methyl glycosides, ,, thioglycosides, glycosyl imidates, − glycosyl phosphates, ,, and glycals, , have been used in combination with suitable activators (Scheme ).…”

“…In 2016, Lee and co-workers synthesized aciculatin (Scheme ). The initial C -glycoside bond formation was achieved by the reaction of thioglycoside 636 and phenol 623 in the presence of NIS and TfOH, giving C -glycoside 637 . A similar transformation as that stated earlier afforded aciculatin.…”

“…In 2016, Lee and co-workers synthesized aciculatin (Scheme 169). 124 The initial C-glycoside bond formation was achieved by 396,397 Chafurosides A and B were obtained from the extracts of oolong tea, sharing an aryl C-glycoside structure with a dihydrofuran ring (Figure 36). 398 Nakatsuka et al reported the first total synthesis of chafuroside A (Scheme 174), 93 which started with the reaction of glycosyl fluoride 653 and phloroacetophenone derivative 646 promoted by BF 3 •OEt 2 , giving β-C-glycoside 654.…”

Advances on Synthesis of Flavonoid Glycosides

“…而金催化的邻炔基 苯甲酸糖基酯法由于它们参与形成强的分子内氢键, 使 得黄酮类 5-OH 反应活性大大提高, 从而实现了黄酮 [71,72] 、抗炎 [73] 等活性, 然而其 在植物中含量极低, 从干燥的竹节草根和根茎提取分离 获得的刺果素苷产率仅为 0.26% [71] , 其化学合成受到了 化学家重视. 文献报道, 首先通过在 NIS/TfOH 酸性条 件下, 2-羟基-4,6-二甲氧基苯乙酮(64)与 α/β 构型洋地黄 毒糖糖基供体通过 Fries 型 O→C 重排反应构建 C-芳基 糖苷键, 得到关键中间体 α-羟基芳基 C-糖苷 (65), 然后 以 EDC/DMAP 介导、催化与 4-苄氧基苯甲酸进行酯化 反应, 再通过 BK-VK 重排得到 β-丙二酮中间体 (67), 以 CSA 介导环化脱水反应构建黄酮结构单元, 最后去苄 基 化 和 苯 甲 酰 基 化 合 成 了 刺 果 素 苷 (69), 总 收 率 为 8.3% [74] (Scheme 12).…”

Total Syntheses and Anti-inflammatory Evaluations of Pongamosides A–C, Natural Furanoflavonoid Glucosides from Fruit of Pongamia pinnata (L.) Pierre

“…Compound 13 was then converted into flavone 14 (89% in two steps) using a catalytic amount of concentrated HCl in AcOH at 110 °C. 10 The preliminary examination of the deprotection of 14 under a H 2 atmosphere showed that the reaction did proceed in the presence of Pd/C or Pd(OH) 2 / C, 11 but the yield of 5a from 14 is very modest (<20%) even if the reaction time was extended to 3 days. We subsequently tested the HCl/AcOH (v/v = 1/2) deprotection system, which generated the desired flavone 5a in a satisfactory yield (75%).…”