title: Rhodium-Catalyzed [3 + 2] Annulation of Cyclic N-Acyl Ketimines with Activated Olefins: Anticancer Activity of Spiroisoindolinones.
abstract: The rhodium(III)-catalyzed redox-neutral coupling reaction of N-acyl ketimines generated in situ from 3-hydroxyisoindolinones with various activated olefins is described. This approach leads to the synthesis of bioactive spiroisoindolinone derivatives in moderate to high yields. In the case of internal olefins such as maleimides, maleates, fumarates, and cinnamates, spiroindanes were obtained by the [3 + 2] annulations reaction. In sharp contrast, acrylates and quinones displayed the β-H elimination followed by Prins-type cyclization furnishing spiroindenes. The synthetic compounds were evaluated for in vitro anticancer activity against androgen-sensitive human prostate adenocarcinoma cells (LNCaP), human prostate adenocarcinoma cells (DU145), human endometrial adenocarcinoma cells (Ishikawa), human breast cancer cell (MCF-7), and triple negative human breast cancer cells (MDA-MB-231). Notably, quinone-containing spiroindenes displayed potent anticancer activity about 2- to 3-fold stronger than that of anticancer agent doxorubicin.
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Satyasheel
authors.initials: S
authors.lastname: Sharma
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Yongguk
authors.initials: Y
authors.lastname: Oh
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Neeraj Kumar
authors.initials: NK
authors.lastname: Mishra
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Umasankar
authors.initials: U
authors.lastname: De
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Hyeim
authors.initials: H
authors.lastname: Jo
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Richa
authors.initials: R
authors.lastname: Sachan
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Jung
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Republic of Korea.
authors.forename: In Su
authors.identifier: 0000-0002-2665-9431
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007097:Imines / Q000737:chemistry*; D054833:Isoindoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000475:Alkenes; D000970:Antineoplastic Agents; D007097:Imines; D054833:Isoindoles; D009570:Nitriles; D013141:Spiro Compounds; C542835:ketimine; D012238:Rhodium