Abstract:
The chromone alkaloid rohitukine, isolated from the Indian medicinal plant Dysoxylum binectariferum have inspired many synthetic analogues that have reached or in the process of reaching the market as anti-cancer drugs. Recently, in 2019, researchers from CSIR-Indian Institute of Integrative Medicine (Jammu) and Indian Pharmacopeia Commission (Ghaziabad) have identified IIIM-290, a synthetic derivative of rohitukine as a strong inhibitor of CDK-9 protein (IC50 = 1.9 nM, the strongest till now) and cell growth (GI50 < 1μM). This makes IIIM-290 a molecule with strong anti-cancer properties. A complete pre-clinical trial of IIIM-290 shows 71% oral bioavailability whereas all previous rohitukine-derived drugs are intravenously bioavailable. This makes IIIM-290 the strongest and the only orally bioavailable Cdk-9 inhibitor among rohitukine derived leads. Although several syntheses of rohitukine-derived drugs and compounds are present in literature, total synthesis of IIIM-290 has not yet been reported. In this work, we have attempted to synthesize IIIM-290 using simple commercially available starting materials. The chromone moiety present in the molecule has been synthesized successfully and several strategic and tactical approaches are presented and discussed.
