ABSTRACT
A remote electronic effect of chiral aminoindanol-derived N-heterocyclic carbene catalyst on an asymmetric benzoin reaction was investigated. The catalyst bearing remote electron-withdrawing substituents increased enantioselectivity of the reaction at the cost of the reaction rate. DFT calculations rationalized the increased enantioselectivity.
Subject(s)
Benzoin , Methane , Stereoisomerism , CatalysisABSTRACT
The total synthesis of 1,4a-di-epi-ent-pancratistatin, a novel stereoisomer of the anti-tumor Amaryllidaceae alkaloid pancratistatin, was achieved in 14 steps starting from D-mannitol. The construction of the pancratistatin skeleton involved conjugate addition of organocuprate to a nitrosoolefin, which was generated in situ from inosose oxime. This was followed by stereoselective reduction of the oxime to an amine and site-selective formylation. Biological evaluations revealed that the newly synthesized compounds exhibit cytotoxicity toward cancer cells and significant ferroptosis inhibitory activity. These compounds constitute a promising small-molecule library for the development of potent bioactive agents.
Subject(s)
Amaryllidaceae Alkaloids , Amaryllidaceae Alkaloids/chemistry , Amaryllidaceae Alkaloids/pharmacology , Amaryllidaceae Alkaloids/chemical synthesis , Humans , Stereoisomerism , Cell Line, Tumor , Isoquinolines/chemistry , Isoquinolines/pharmacology , Isoquinolines/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Drug Screening Assays, Antitumor , Molecular Structure , Cell Proliferation/drug effects , Structure-Activity Relationship , Cell Survival/drug effectsABSTRACT
The remote electronic effects of chiral N-heterocyclic carbene catalysts on the asymmetric intramolecular Stetter reaction are investigated. The reaction rate and enantioselectivity were markedly influenced by a substituent at a remote position of the catalyst. The absolute configurations of the products are revised on the basis of X-ray diffraction. Density-functional theory calculations rationalize the improvement of the enantioselectivity using an electron-deficient catalyst.