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).
Homologation of α-amino acids to β-amino acids using Boc2O
Vasanthakumar, Ganga-Ramu,Patil, Basanagoud S.,Suresh Babu, Vommina V.
, p. 2087 - 2089 (2002)
The use of Boc2O as a coupling agent in the homologation of N-urethane protected-α-amino acid to its β-homomers by the Arndt-Eistert method is described. The homologation gives good yields without racemization. The use of Boc2O as a
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.
Iminium ion-enamine cascade cyclizations: Facile access to structurally diverse azacyclic compounds and natural products
Hanessian, Stephen,Chattopadhyay, Amit Kumar
supporting information, p. 232 - 235 (2014/01/23)
A one-pot, mild, two-component iminium ion-enamine cascade reaction to construct structurally diverse azacyclic frameworks from l-proline and l-pipecolic acid, and its application to indolizidine and quinolizidine alkaloids and azasteroids, is reported.
CuI-promoted one-pot synthesis of N-boc protected β-ketotriazole amino acids: Application in the synthesis of new class of dipeptidomimetics
Vishwanathaa,Narendra,Sureshbabu, Vommina V.
, p. 308 - 314 (2012/07/17)
One-pot click chemistry of Nα-Boc-bromomethylketones, NaN3 and propiolic acid affords N-Boc protected 1,4- disubstituted 1,2,3-β-ketotriazole acids in good to excellent yield. The use of CuI as catalyst and DMSO as solvent leads the click react
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
Synthesis of 6- and 7-membered cyclic enaminones: Scope and mechanism
Niphakis, Micah J.,Turunen, Brandon J.,Georg, Gunda I.
supporting information; experimental part, p. 6793 - 6805 (2010/12/20)
Six- and seven-membered cyclic enaminones can be prepared using common, environmentally benign reagents. Amino acids are used as synthetic precursors allowing diversification and the incorporation of chirality. The key reaction in this multistep process involves deprotection of Boc-amino ynones and subsequent treatment with methanolic K2CO3 to induce cyclization. A β-amino elimination side reaction was identified in a few labile substrates that led to either loss of stereochemical purity or degradation. This process can be mitigated in specific cases using mild deprotection conditions. NMR and deuterium-labeling experiments provided valuable insight into the workings and limitations of this reaction. Although disguised as a 6-endo-dig cyclization, the reagents employed in the transformation play a direct role in bond-making and bond-breaking, thus changing the mode of addition to a 6-endo-trig cyclization. This method can be used to construct an array of monocyclic and bicyclic scaffolds, many of which are found in well-known natural products (e.g., indolizidine, quinolizidine, and Stemona alkaloids).
Total syntheses of arylindolizidine alkaloids (+)-ipalbidine and (+)-antofine
Niphakis, Micah J.,Georg, Gunda I.
supporting information; experimental part, p. 6019 - 6022 (2010/12/19)
This paper presents the first application of two recently developed reactions to natural product synthesis. The first method involves a 6-endo-trig cyclization to prepare a versatile chiral enaminone building block. The second is a direct C-H arylation reaction. As a showcase for the utility of these methods, (+)-antofine and (+)-ipalbidine were synthesized in only 8 steps and 24-26% overall yields.
5-(2-Pyrrolidinyl)oxazolidinones and 2-(2-pyrrolidinyl)benzodioxanes: Synthesis of all the stereoisomers and α4β2 nicotinic affinity
Pallavicini, Marco,Bolchi, Cristiano,Binda, Matteo,Cilia, Antonio,Clementi, Francesco,Ferrara, Rossana,Fumagalli, Laura,Gotti, Cecilia,Moretti, Milena,Pedretti, Alessandro,Vistoli, Giulio,Valoti, Ermanno
scheme or table, p. 854 - 859 (2009/08/15)
The four stereoisomers of 2-oxazolidinone 5-substituted with 1-methyl-2-pyrrolidinyl (1), of 1,4-benzodioxane 2-substituted with the same residue (2) and of the nor-methyl analogue of this latter (2a) were synthesized as candidate nicotinoids. Of the 12 c
