- The synthesis of α,α-disubstituted α-amino acids via ichikawa rearrangement
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An approach to α,α-disubstituted α-amino acids is reported. The key step is allyl cyanate-to-isocyanate rearrangement. As demonstrated, the resultant allyl isocyanates can be directly trapped with various nucleophiles, for instance, alcohols, amines, and organometallic reagents, to provide a broad range of N-functionalized allylamines. The developed method has been successfully applied in the synthesis of two bioactive peptides: 2-aminoadamantane-2-carboxylic acid derived P2X7-evoked glutamate release inhibitor and 4-amino-tetrahydropyranyl-4-carboxylic acid derived dipeptide GSK-2793660, which is currently in clinical trials as cathepsin C inhibitor for the treatment of cystic fibrosis, noncystic fibrosis bronchiectasis, ANCA-associated vasculitis and bronchiectasis.
- Szczes?niak, Piotr,Pieczykolan, Micha?,Stecko, Sebastian
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p. 1057 - 1074
(2016/02/19)
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- Synthesis and evaluation of C8-substituted 4.5-spiro lactams as Glycogen Phosphorylase a inhibitors
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An effective synthesis of 4.5-spiro lactams 28/29, has been completed in nine steps with an overall yield of 5.8%. The 4.5-spiro lactams were made from 2-allyl-Cbz-Pro-OMe 21, which was converted into the corresponding alcohol 22 via a hindered borane reaction with (2-methylbutyl)2borane. Subsequent Swern oxidation of 22 gave novel aldehyde 23. Aldehyde 23 was treated under Bucherer-Bergs reaction conditions to give hydantoin 26, which was opened to the corresponding amino acid 30 using di-tert-butyl dicarbonate and DMAP followed by hydrolysis. Treatment of amino acid 30 with acidic methanol gave 4.5-spiro lactams 28/29. Only 4.5-spiro lactam 29 displayed moderate activity against GPa with an IC50 of 241 μM.
- Loughlin, Wendy A.,Schweiker, Stephanie S.,Jenkins, Ian D.,Henderson, Luke C.
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supporting information
p. 1576 - 1582
(2013/03/29)
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- 1-Aminocylopropane-1-carboxylic acid derivatives as ligands at the glycine-binding site of the N-methyl-D-aspartate receptor
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Several 1-aminocyclopropane-1-carboxylic acid derivatives were prepared and tested for activity at the glycine-binding site of the N-methyl-D- aspartate (NMDA) receptor complex. Structural modifications involved the amino group, the carboxylic function or
- Balsamini, Cesarino,Bedini, Annalida,Spadoni, Gilberto,Tarzia, Giorgio,Tontini, Andrea,Balduini, Walter,Cimino, Mauro
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p. 181 - 188
(2007/10/03)
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- Facile new method for preparation of optically active protected proline
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Treatment of L-N-protected 2-amino-5-bromopentanoic acid ester, which was prepared from protected L-glutamic acid, with sodium hydride in tetrahydrofuran (THF) proceeded to give the corresponding protected L-proline in high yield. On the other hand, the reaction of 2-aminobutyric acid derivative with sodium hydride gave the 1-aminocyclopropane-1-carboxylic acid derivative.
- Yamaguchi, Jun-Ichi,Ueki, Masaaki
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p. 621 - 622
(2007/10/03)
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- A Simple Synthesis of 1-Aminocyclopropane-1-carboxylic Acid
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Conversion of N-carbobenzyloxy-L-glutamic acid α-methylester (Z-L-glu(OH)OCH3, 1) into the bromo derivative 2 and subsequent γ-elimination by the use of sodium hydride leads to the fully protected synthon 3 in good yields.Deprotection by sodium hydroxide and hydrogenolysis yields almost quantitively the key substance 5.
- Strazewski, Peter,Tamm, Christoph
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p. 298 - 299
(2007/10/02)
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