101130-03-4Relevant articles and documents
Continuous flow synthesis of α-halo ketones: Essential building blocks of antiretroviral agents
Pinho, Vagner D.,Gutmann, Bernhard,Miranda, Leandro S. M.,De Souza, Rodrigo O. M. A.,Kappe, C. Oliver
, p. 1555 - 1562 (2014)
The development of a continuous flow process for the multistep synthesis of α-halo ketones starting from N-protected amino acids is described. The obtained α-halo ketones are chiral building blocks for the synthesis of HIV protease inhibitors, such as atazanavir and darunavir. The synthesis starts with the formation of a mixed anhydride in a first tubular reactor. The anhydride is subsequently combined with anhydrous diazomethane in a tube-in-tube reactor. The tube-in-tube reactor consists of an inner tube, made from a gas-permeable, hydrophobic material, enclosed in a thick-walled, impermeable outer tube. Diazomethane is generated in the inner tube in an aqueous medium, and anhydrous diazomethane subsequently diffuses through the permeable membrane into the outer chamber. The α-diazo ketone is produced from the mixed anhydride and diazomethane in the outer chamber, and the resulting diazo ketone is finally converted to the halo ketone with anhydrous ethereal hydrogen halide. This method eliminates the need to store, transport, or handle diazomethane and produces α-halo ketone building blocks in a multistep system without racemization in excellent yields. A fully continuous process allowed the synthesis of 1.84 g of α-chloro ketone from the respective N-protected amino acid within ～4.5 h (87% yield).
Studies towards the preparation of sparteine-like diamines for asymmetric synthesis
Harrison, Justin R.,O'Brien, Peter,Porter, David W.,Smith, Neil M.
, p. 3623 - 3631 (1999)
A route for the preparation of sparteine-like diamines starting from naturally occurring amino acids has been explored. Starting from the amino acids (S)-proline and (S)-phenylalanine, two novel sparteine-like diamines 2 and 3 have been prepared. The synthetic route involves Dieckmann condensation followed by a double Mannich reaction to set up the tricyclic structure with control of the relative stereochemistry. During the Dieckmann and Mannich reactions it was found that racemisation occurred either via retro-Michael or retro-Mannich processes. Conditions for preventing racemisation in the Dieckmann reaction were uncovered but it was not possible to prevent racemisation during the double Mannich reaction. Thus, the two novel sparteine-like diamines 2 and 3 have been prepared in racemic form. The Royal Society of Chemistry 1999.
Continuous flow synthesis of β-amino acids from α-amino acids via Arndt-Eistert homologation
Pinho, Vagner D.,Gutmann, Bernhard,Kappe, C. Oliver
, p. 37419 - 37422 (2014/12/09)
A fully continuous four step process for the preparation of β-amino acids from their corresponding α-amino acids utilizing the Arndt-Eistert homologation approach is described. the Partner Organisations 2014.
Kinetic deconjugation: A gateway to the synthesis of Xxx-Gly (E)-alkene dipeptide isosteres
Proteau-Gagné, Arnaud,Nadon, Jean-Franois,Bernard, Sylvain,Guérin, Brigitte,Gendron, Louis,Dory, Yves L.
supporting information; experimental part, p. 6603 - 6605 (2012/02/03)
A new method for the preparation of Xxx-Gly (E)-alkene dipeptide isosteres (EADIs), using LDA deprotonation followed by 1 N HCl quench, was explored. The method, named kinetic deconjugation, enabled the synthesis of Tyr-Gly, Gly-Gly, Ser-Gly, Pro-Gly, and
