Total synthesis of (±)−jolkinolide A, B, and E utilizing a new mild esterification followsd by intramolecular Wittig-Horner reaction

Synthesis of Novel 3,19-Dihydroxyjolkinolides and Related Derivatives Starting from Andrographolide

“…Construction of the D ring, including the γ-ylidenebutenolide moiety, was anticipated from 10 through an intramolecular Wittig-Horner reaction developed by Katsumura and coworkers. 14 We also reported this method in two recent articles. 7,8 Compound 10 could be acquired from 11 in a single maneuver via direct oxygenation, while compound 11 could be readily prepared from 12 by bis-hydroxy protection.…”

Efficient Synthesis of Jolkinolides A and B from Steviol

“…The structure of jolkinolides A and B Katsumura et al 5 firstly accomplished the total synthesis of (±)-jolkinolides A, B, and E starting from 10-(methoxycarbonyl)-β-ionone through almost twenty steps, which gave a low yield of the target products. Herein, we describe a concise and scalable approach to the synthesis of jolkinolides A and B from an easily available material, steviol (6).…”

“…Herein, we describe a concise and scalable approach to the synthesis of jolkinolides A and B from an easily available material, steviol (6). Our retrosynthetic analysis is shown in Scheme 1, the construction of γ-ylidenebutenolide moiety was anticipated from diosphenol 3 through the intramolecular Wittig-Horner reaction developed by Katsumura et al 5 We envisioned that diosphenol 3 would be available in a single maneuver via the direct oxygenation of 4, which would be prepared from 5 through stereoselective epoxidation. In the structure of steviol (6), the A/B ring is trans fused, at C4 there are β-methyl and α-carboxy groups, at C10 there is an α-methyl group, and at C5 and C9 there are β-H, which almost exactly matches those of our target compounds in the structural framework.…”

“…The combined organic layers were washed with brine, dried (anhyd Na 2 SO 4 ), filtered, and evaporated to dryness to give a residue that was purified by flash chromatography (silica gel, PE-EtOAc, 15:1) to give jolkinolide A (1) (0.13 g, 0.41 mmol, 84%) as a white amorphous solid; mp 218-219 °C [Lit. 5…”

Efficient Synthesis of Novel Jolkinolides and Related Derivatives Starting from Stevioside

“…4 It was reported that the molecular target and mode of action of abietane lactones were inhibition the activation of NF-kB signaling pathway and JAK/STAT signaling pathway, and induced apoptosis of tumor cells. 5 Katsumura et al 6 carried out the total synthesis of (±)jolkinolides A, B, and E starting from 10-(methoxycarbonyl)-b-ionone through a synthetic route of almost twenty reaction steps and bearing a low yield to obtain the target compounds. Herein, we simply modified the synthetic route using easily available and low-cost stevioside as our starting material, and developed a facile access to obtain the target compounds (Scheme 1).…”