title: Meeting Organocatalysis with Drug Discovery: Asymmetric Synthesis of 3,3'-Spirooxindoles Fused with Tetrahydrothiopyrans as Novel p53-MDM2 Inhibitors.
abstract: An organocatalytic enantioselective Michael-Michael cascade reaction is developed for the synthesis of chiral spirotetrahydrothiopyrans. This highly functionalized scaffold was assembled in moderate to good yield (55-74%) and excellent diastereo- and enantioselectivities (>30:1 dr, ≥ 99% ee) with the creation of four consecutive stereogenic centers. The novel spiro-oxindole scaffold is validated as a new class of p53-MDM2 protein-protein interaction inhibitors with good antitumor activity.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, People's Republic of China.|Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University , 169 Changle West Road, Xi'an, 710032, P.R. China.
authors.forename: Shengzheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Shanchao
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D055808:Drug Discovery; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D000078183:Oxindoles; D051736:Proto-Oncogene Proteins c-mdm2 / Q000187:drug effects*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D000078183:Oxindoles; D013141:Spiro Compounds; D016159:Tumor Suppressor Protein p53; C022960:2-oxindole; D051736:Proto-Oncogene Proteins c-mdm2