A highly regioselective, one-step lipase-catalyzed method enabled the diversification of rapamycin at its C42 position, producing 10 derivatives (4 novel). Biological screening identified derivative 9 as a potent lead compound with superior antiproliferative activity (IC50 = 6.5 μM in ACHN cells), outperforming both rapamycin and temsirolimus. This work offers a practical enzymatic route for rapamycin remodeling and highlights a promising mTOR-targeted anticancer candidate.
Liu et al. (Tue,) studied this question.