1129634-44-1Relevant articles and documents
An enantioselective approach to 4-substituted proline scaffolds: Synthesis of (s)-5-(tert-butoxy carbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid
Ariza, Xavier,Bartra, Martí,Berenguer, Ramon,Gómez, Roberto,Garcia, Jordi,López, Blanca,Torralvo, Hèctor
, (2020)
A catalytic and enantioselective preparation of the (S)-4-methyleneproline scaffold is described. The key reaction is a one-pot double allylic alkylation of an imine analogue of glycine in the presence of a chinchonidine-derived catalyst under phase transfer conditions. These 4-methylene substituted proline derivatives are versatile starting materials often used in medicinal chemistry. In particular, we have transformed tert-butyl (S)-4-methyleneprolinate (12) into the N-Boc-protected 5-azaspiro[2.4]heptane-6-carboxylic acid (1), a key element in the industrial synthesis of antiviral ledipasvir.
Development of potent and selective Cathepsin C inhibitors free of aortic binding liability by application of a conformational restriction strategy
Banerjee, Abhisek,Behera, Dayanidhi B.,Chakraborti, Samitabh,Das, Sanjib,Gharat, Laxmikant A.,Iyer, Pravin S.,Kadam, Pradip,Karanjai, Keya,Patil, Sandip,Pawar, Mahesh,Qadri, Mohammad Mohsin,Saini, Jagmohan S.,Velagaleti, Ranganadh,Yadav, Pravin
, (2021/06/25)
Cathepsin C plays a key role in the activation of several degradative enzymes linked to tissue destruction in chronic inflammatory and autoimmune diseases. Therefore, Cathepsin C inhibitors could potentially be effective therapeutics for the treatment of diseases such as chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome (ARDS). In our efforts towards the development of a novel series of Cathepsin C inhibitors, we started working around AZD5248 (1), an α-amino acid based scaffold having potential liability of aortic binding. A novel series of amidoacetonitrile based Cathepsin C inhibitors were developed by the application of a conformational restriction strategy on 1. In particular, this work led to the development of a potent and selective Cathepsin C inhibitor 3p, free of aortic binding liability.
Preparation method of (S)-5-(tert-butyloxycarbonyl)-5-azaspiro [2, 4] heptane-6-carboxylic acid
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Paragraph 0066-0068, (2020/07/13)
The invention relates to the technical field of organic synthesis. The invention specifically relates to a preparation method of an antiviral drug ledipasvir chiral intermediate (S)-5-(tert-butyloxycarbonyl)-5-azaspiro [2, 4] heptane-6-carboxylic acid. The preparation method comprises the following steps: condensing 5-(tert-butyloxycarbonyl)-5-azaspiro [2.4] heptane-6-carboxylic acid racemate anda chiral amine resolution reagent to obtain amides (I) and (II); hydrolyzing the compound (I) to obtain a target compound (S)-5-(tert-butyloxycarbonyl)-5-azaspiro [2.4] heptane-6-carboxylic acid (III), hydrolyzing the compound (II) to obtain an enantiomer (IV), removing Boc from the compound (IV), performing configuration conversion to obtain a compound (VII), and performing amino protection on the compound (VII) to obtain the target compound (III). The invention provides a simple and convenient cost-reducing industrial production route for the chiral intermediate of the antiviral drug ledipasvir, and has the advantages of simple reaction operation, high chiral resolution yield and lower cost.