Asymmetric Synthesis of N-Fmoc-(S)-7-aza-tryptophan via Alkylation of Chiral Nucleophilic Glycine Equivalent

Ni(II)-complexes, derived from glycine Schiff bases with chiral tridentate ligands, have been used as powerful tools for the synthesis of structurally diverse tailor-made amino acids. In this manuscript, asymmetric alkylation reaction between chiral nucleophilic glycine derived Ni-complex and 3-(chloromethyl)-1H-pyrrolo[2,3-b]pyridine has been developed under convenient conditions, which affords the corresponding alkylated Ni-complex in 74 % yield and excellent diastereoselectivity (only one isomer). This reaction features convenient conditions and completely controlled diastereoselectivity, which provides a highly valuable approach for asymmetric synthesis of 7-aza-tryptophan

Next generation organofluorine containing blockbuster drugs

Funding: the National Natural Science Foundation of China (No. 21761132021), the Hungarian Research Foundation (NKFIH No. K 119282), and Ministry of Human Capacities, Hungary grant 20391-3/2018/FEKUSTRAT. The Qinlan Project of Jiangsu Province, and IKERBASQUE, the Basque Foundation for Science are also acknowledged.The role of organo-fluorine compounds in modern health, food and energy related industries is widely-appreciated. The unique properties that fluorine imparts to organic molecules, stemming from its high electronegativity and stability when bound to carbon, finds it increasing being used in the development of new bioactivities. Around 25% of the current blockbuster drugs contain fluorine and this number is increasing to well above 30% for recent FDA approvals. In this Review we highlight a selection of the most successful organo-fluorine drugs, that have achieved blockbuster status, namely, sitagliptin (diabetes), sofosbuvir (hepatitis C), emtricitabine (HIV), glecaprevir/pibrentasvir (hepatitis C), elvitegravir (HIV), dolutegravir (HIV), bictegravir (HIV), efavirenz (HIV), enzalutamide (prostate cancer), aubagio (immunomodulatory) and paliperidone palmitate (schizophrenia). For each compound we discuss their discovery, their relevant disease state and how they are made, emphasizing the source of fluorine-containing moieties, and where known, their mode of action.PostprintPeer reviewe

Asymmetric Synthesis of Tailor-Made Amino Acids Using Chiral Ni(II) Complexes of Schiff Bases. An Update of the Recent Literature

Tailor-made amino acids are indispensable structural components of modern medicinal chemistry and drug design. Consequently, stereo-controlled preparation of amino acids is the area of high research activity. Over last decade, application of Ni(II) complexes of Schiff bases derived from glycine and chiral tridentate ligands has emerged as a leading methodology for the synthesis of various structural types of amino acids. This review article summarizes examples of asymmetric synthesis of tailor-made α-amino acids via the corresponding Ni(II) complexes, reported in the literature over the last four years. A general overview of this methodology is provided, with the emphasis given to practicality, scalability, cost-structure and recyclability of the chiral tridentate ligands.This research was funded by the National Natural Science Foundation of China (No. 21761132021), and IKERBASQUE, Basque Foundation for Science

Asymmetric Synthesis of N

Ni(II)-complexes, derived from glycine Schiff bases with chiral tridentate ligands, have been used as powerful tools for the synthesis of structurally diverse tailor-made amino acids. In this manuscript, asymmetric alkylation reaction between chiral nucleophilic glycine derived Ni-complex and 3-(chloromethyl)-1H-pyrrolo[2,3-b]pyridine has been developed under convenient conditions, which affords the corresponding alkylated Ni-complex in 74 % yield and excellent diastereoselectivity (only one isomer). This reaction features convenient conditions and completely controlled diastereoselectivity, which provides a highly valuable approach for asymmetric synthesis of 7-aza-tryptophan