Efficient Total Synthesis and Biological Activities of 6‐Deoxyisojacareubin

Abstract

6-Deoxyisojacareubin was directly synthesized in a six-step route with an overall yield of about 20%. In this route, the excellent site selectivity of this Claisen rearrangement-cyclization reaction cascade was achieved by inserting a bulky p-tosyl group into the free 1-OH, and in the last step, some efficient demethylation methods were explored. Furthermore, all synthesized intermediates including 6-deoxyisojacareubin were evaluated for their inhibitory activity against the QGY-7703 cell line. Of these, compound 1 and 6-deoxyisojacareubin showed moderate activities with IC50 values of 39.61 and 9.65 µM, respectively, when compared to the positive control 5-fluorouracil with an IC50 value of 11.24 µM. Further investigation using non-radioactive detection of protein kinase C (PKC) suggested that these two compounds possessed potency in the inhibition of PKC.

Inhibition of protein kinase C by isojacareubin suppresses hepatocellular carcinoma metastasis and induces apoptosis in vitro and in vivo

“…For ISJ synthesis, the construction of the xanthone nucleus and the benzopyran ring were performed based on our previous work 33 34 . The retrosynthetic analysis of ISJ is outlined in Fig.…”

“…In our previous studies, a new series of derivatives of phenyl-substituted polyoxygenated xanthone were synthesized and evaluated for in vitro cytotoxicity against HCC cells and hepatocytes 33 34 . In the present study, ISJ and compound 7 demonstrated potency at several cellular-level activities, thereby supporting the derivatives’ antitumor effects.…”

“…The cell viability assay was performed as previously reported using a Cell Counting Kit-8 (CCK-8; Dojindo, Kumamoto, Japan) 33 34 . The relative cell viability was presented as % inhibition and calculated using the following formula:…”

“…The PKC activity assay was carried out as previously reported 33 , according to the instructions of the PepTag non-radioactive PKC assay kit (Promega) 60 . The bands were photographed using the Syngene GBOX-iCHEMI-XR system, and the phosphorylated bands were cut out for quantification measurement at 570 nm.…”

Design of a Functional Chromene‐Type Kobayashi Precursor: Gram‐Scale Total Synthesis of Natural Xanthones by Highly Regioselective Aryne Annulation

“…The 2,2‐dimethyl‐2 H ‐chromene motif is widely found in natural products [1] as bioactive fragments, such as 6‐deoxyisojacareubin (anti‐tumor), [2] inophyllum B (anti‐HIV), [3] deguelin (ubiquinone oxidoreductase) [4] and pongapinone A (anti‐inflammatory) [5] (Figure 1). Due to their promising biological activities, the development of practical synthetic methodologies to chromene fragments has attracted considerable interest [6] .…”