An asymmetric three-component reaction of diazo compounds and alcohols with imines catalyzed cooperatively by a rhodium complex and a chiral Brønsted acid provides a general and efficient entry to beta-amino-alpha-hydroxyl acid derivatives in high yields with excellent stereoselectivities.

Development of multidrug resistance (MDR) during chemotherapy is a fundamental obstacle associated with cancer care. Prior studies have identified (2-(4-methoxyphenyl)-4-quinolinyl)(2-piperidinyl)methanol (5) (NSC23925) to be a small molecule agent that reverses MDR in cancer cells. We synthesized all four isomers of 5 and analyzed them by liquid chromatography-mass spectrometry (LCMS). Structure-activity relationships for reversing MDR were evaluated. Isomer 11 demonstrated the most potent activity. 11 reversed MDR in several drug-resistant cell lines expressing Pgp, including ovarian, breast, colon, uterine, and sarcoma cancer. 11 resensitized these cell lines to paclitaxel, doxorubicin, mitoxantrone, vincristine, and trabectedin with no effect on cell sensitivity to cisplatin, topotecan, and methotrexate. 11 significantly enhanced in vivo antitumor activity of paclitaxel in MDR xenograft models, without increasing the level of paclitaxel toxicity. In conclusion, 11 and derivatives of this compound may hold therapeutic value in the treatment of MDR-dependent cancers.

The 3-substituted 3-hydroxyindolin-2-ones with adjacent quaternary stereocenters were constructed in a single step via an efficient and stereoselective trapping of oxonium ylide with isatins. This reaction proceeds well in supercritical CO2 and is an example of the ability to use green approaches to efficiently construct polyfunctional molecules.

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