First Synthesis of Bioactive Diphyllin Glycosides Isolated from Justicia patentiflor Hemsl

Abstract

The syntheses of three naturally occurring diphyllin glycosides have been achieved. 7-O-β-D-Quinovopyranosyldiphyllin (patentiflorin A) and 7-O-β-L-fucopyranosyldiphyllin (patentiflorin B) were synthesized by the glycosylation of diphyllin with peracetylglycosyl bromides under phase transfer catalysis (PTC) conditions. 4"-O-Acetyl-7-O-β-L-fucopyranosyldiphyllin (4"-O-acetyl patentiflorin B) was obtained from patentiflorin B on an orthoesterification-orthoester rearrangement approach. Their 1 H NMR, 13 C NMR and HRMS signals are all consistent with those reported for the natural product.

First Total Synthesis of the Bioactive Arylnaphthyl Lignan 4‐O‐Glycosides Phyllanthusmin D and 4′′‐O‐Acetylmananthoside B

“…With ample amounts of the diphyllin aglycon in hand, the synthesis of phyllanthusmin D ( 1 ) was investigated (Scheme ). Phase‐transfer‐catalysis (PTC) glycosylation between diphyllin ( 4 ) and perbenzoylated l ‐arabinosyl bromide 5 proceeded smoothly with NaOH (0.1 n ) as promoter and TBAB (tetrabutylammonium bromide) as phase‐transfer catalyst,, and diphyllin 4‐ O ‐glycoside 6 was formed in a good 84 % yield. The formation of an α‐configured glycosidic linkage was governed by S N 2 substitution, and the configuration was confirmed by the appearance of a signal of the anomeric proton of the l ‐arabinosyl residue in the 1 H NMR spectrum at δ = 5.43 ppm with a diagnostic coupling constant value of 6.4 Hz.…”

“…The highly antiproliferative activity, the new mechanism of action, and the structural superiority make arylnaphthyl glycosides more attractive to both biologists and synthetic chemists. The seminal synthetic work of Li et al and Zhao et al resulted in the synthesis of a few naturally occurring arylnaphthyl glycosides and their analogues. This greatly facilitates the investigation of structure–activity relationships.…”

Synthesis, Docking Studies and Anticancer Activity of New Substituted Pyrimidine and Triazolopyrimidine Glycosides

“…A variety of pyrimidine derivatives fused with other heterocycles has been found as anticancer agents used in clinics or in clinical trials (VanderWel et al, 2005;Toogood et al, 2005;Palmer et al, 2005;Malagu et al, 2009;Zhao et al, 2007;Hafez and El-Gazzar, 2009;Shawali et al, 2010). Derivatives of the [1,2,4] triazolo [4,3-a]pyrimidine ring system have been revealed to possess antitumor activity Hafez and El-Gazzar, 2009;Shawali et al, 2010).…”

“…Synthesized glycosides and their derived analogs (Zhao et al, 2008;Zhao and Li, 2007) revealed considerable inhibitory activity of DNA-topoisomerase II (TopoII) that controls DNA topology by transitory cleavage of the DNA double helix, which was affirmed as important molecular target of anticancer drugs (Champoux, 2001;Pommier et al, 2010). Moreover, studied biological assays found that exotic sugar part confers a number of glycosides with best conformation possessing high binding affinities via hydrogen bonding to the entry of the ATPase pocket (Gui et al, 2011;Shi et al, 2012).…”

Synthesis, Cytotoxicity and Pro-apoptosis of Novel Benzoisoindolin Hydrazones as Anticancer Agents

“…9,10) Previously, we have successfully synthesized several natural diphyllin glycosides and their analogues. 11,12) Biological results showed that they were effective apoptosis inducers and cell proliferation inhibitors, which encouraged us to synthesize more compounds to fully discuss the SAR of diphyllin. To our best knowledge, there is no such effort addressed to modify the lactone moitey of diphyllin.…”