Fig. 1
From: CRO-67 has anti-cancer activity in pancreatic tumor cells and stromal cancer-associated fibroblasts
Synthesis of CRO-05, CRO-67, and CRO-68. Synthesis of the racemic CRO-05 1 was performed on multi-gram scale at Jubilant Biosys (Greater Noida, India), which was subsequently separated at ChemPartner Co., Ltd (Shanghai, China) via Supercritical Fluid Chromatography (SFC) to obtain enantiopure (+)-CRO-67 6 and (−)-CRO-68 7. Resorcinol 2, aryl ketone 3, O-acylated coumarin derivative 4, 2H-chromene 5. (i) 4-nitrobenzoylchloride, AlCl3, DCM, 0 to 50 °C, 16 h, 23%; (ii) 3,4-dimethylphenylacetic acid, diisopropylethylamine (DIPEA), Ac2O, 130 °C, 16 h, 31%; (iii) BH3:DMS, THF, 0 °C to room temperature, 16 h, 59%; (iv) Pd/C (cat.), H2 (g, 10 kg/cm2), EtOAc, 45 °C, 16 h, 73%; (v) Supercritical Fluid Chromatography (SFC), (+)-CRO-67, 96%, enantiomeric excess (ee) 99.52%, (−)-CRO-68, 98%, ee 100%.
