105099-19-2Relevant academic research and scientific papers
A chiral pool strategy for the synthesis of enantiopure hydroxymethyl-substituted pyridine derivatives
Eidamshaus, Christian,Reissig, Hans-Ulrich
experimental part, p. 6056 - 6069 (2011/12/15)
A simple procedure for the synthesis of enantiopure hydroxymethyl- substituted pyridine derivatives is presented. The developed method is based on TMSOTf-promoted cyclocondensations of β-ketoenamides, leading to differently substituted 4-hydroxypyridine/4-pyridone derivatives. The required β-ketoenamides were prepared by acylation ofeasily available enamino ketones with suitably protected enantiopure carboxylic chlorides. Most of the experiments were performed with D-mandelic acid as starting material. It has been shown that all steps occur essentially without racemisation. Several of the prepared 4-pyridone derivatives were transformed into the corresponding pyrid-4-yl nonaflates and subjected to a series of palladium-catalysed transformations, such as Suzuki, Heck or Sonogashira reactions. In addition, regioselective side-chain functionalisation of unsymmetrically 2,6-disubstituted pyridine derivatives was accomplished by application of Boekelheide rearrangements of the corresponding pyridine N-oxides. The presented methods allow a flexible, rapid and scalable approach to highly substituted, enantiopure pyridine derivatives. A new route to hydroxymethyl-substituted pyridine derivatives, starting from enantiopure α-hydroxy carboxylic acids, is described. The synthetic value of the method is demonstrated by multifaceted functionalisation reactions of the prepared pyridine derivatives, leading to a series of highly substituted enantiopure pyridine derivatives.
NOVEL CYCLIC BORONATE INHIBITORS OF HCV REPLICATION
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Page/Page column 73-75, (2009/05/29)
Compounds of formula (I) or a salt thereof are provided; wherein R1, R2, R3, R4, R6, R8, R20, R30, Y, Z and n are as defined in the description. Uses of the compounds as medicaments, and in the manufacture of medicaments for treating viral infection, especially HCV infection are also disclosed. The invention further comprises processes to make these compounds and pharmaceutical formulations thereof.
Nα-Fmoc-protected ω-azido- and ω-alkynyl-L- amino acids as building blocks for the synthesis of "clickable" peptides
Isaad, Alexandra Le Chevalier,Barbetti, Francesca,Rovero, Paolo,D'Ursi, Anna Maria,Chelli, Mario,Chorev, Michael,Papini, Anna Maria
experimental part, p. 5308 - 5314 (2009/06/18)
The growing interest in the 1,4-disubstituted-1,2,3-triazolyl moiety as an amide bond surrogate and its formation through very mild, chemoselective, and bioorthogonal CuI-catalyzed Huisgen 1,3-dipolar [3+2] cycloaddition of an alkynyl to an azi
Improved procedures for the synthesis of (S)-2-[N-(N'-benzyl- prolyl)amino]benzophenone (BPB) and Ni(II) complexes of Schiff's bases derived from BPB and amino acids
Belokon', Yuri N.,Tararov, Vitali I.,Maleev, Viktor I.,Savel'eva, Tatiana F.,Ryzhov, Michael G.
, p. 4249 - 4252 (2007/10/03)
(S)-N-Benzylproline (BP) was obtained by the reaction of (S)-proline and benzylchloride in high chemical yield (89%). (S)-2-[N-(N'- Benzylprolyl)amino]benzophenone (BPB) was synthesized in amounts greater than 100 g by the SOCl2 promoted condensation of BP with 2-aminobenzophenone (yield 82%). Ni(II) complexes of Schiff's bases derived from BPB and amino acids were prepared by an improved procedure involving the use of KOH as a base and MeOH as solvent (yield 90-91%).
A NOVEL APPLICATION OF THE CHIRAL REAGENT (S)-2-N-(N'-BENZYLPROLYL)-AMINOBENZALDEHYDE: SYNTHESIS OF OPTICALLY PURE α-METHYLVALINE AND α-METHYLGLUTAMIC ACID
Belokon, Yu. N.,Motsishkite, S. M.,Tararov, V. I.,Maleev, V. I.
, p. 1355 - 1360 (2007/10/02)
The synthesis of α-methyl substituted amino acids using Ni(II) complexes of the Schiff base obtained from alanine and (S)-2-N-(N'-benzylpropyl)aminobenzaldehyde is described.This complex was alkylated with isopropyl bromide, gramine iodomethylate, and methyl acrylate (in a Michael reaction).From the resulting mixtures of products, diastereomerically pure complexes were obtained by crystallization or silica gel chromatography.Both (S)- and (R)-enantiomers of the optically active amino acids α-Me-Val and α-MeGlu were obtained after decomposing the diastereomerically pure complexes.
Asymmetric Synthesis of Threonine and Partial Resolution and Retroracemization of α-Amino Acids via Copper(II) Complexes of Their Schiff Bases with (S)-2-N-(N'-Benzylprolyl)aminobenzaldehyde and (S)-2-N-(N'-Benzylprolyl)aminoacetophenone. Crystal and Molecular Structure of a ...
Belokon', Yu. N.,Zel'tzer, I. E.,Bakhmutov, V. I.,Saporovskaya, M. B.,Ryzhov, M. G.,et al.
, p. 2010 - 2017 (2007/10/02)
The work described here is concerned with the search for universal chiral reagent for the asymmetric synthesis, resolution, and retroracemization of amino acids.Reaction of N-benzyl-(S)-proline with o-aminobenzaldehyde or o-aminoacetophenone has given (S)-2-N-(N'-benzylprolyl)aminobenzaldehyde ((S)-BPAB) or (S)-2-N-(N'-benzylprolyl)aminoacetophenone ((S)-BPAAPh).These chiral reagents have interacted with α-amino acids (aa) and Cu(II) ions to form complexes CuII and CuII in which Schiff bases (S)-BPAB-aa or (S)-BPAAPh-aa act as tetradentate ligands and coordinate the copper ion by the nitrogen atoms of the pyrrolidine fragment, the deprotonated amide group, and the amino acid fragment and by the oxygen atom of the carboxylate.Such a structure was supported by data on elemental analysis, the molecular weight measurements, and electron, IR, and CD spectra.It was finally confirmed by an X-ray diffraction analysis of CuII.One equivalent of (S)-BPAB has reacted with 2 equiv of (R,S)-aa and 2 equiv of Cu(II), having given preferential formation of copper complexes of Schiff bases with (S)-aa.After their extraction with chloroform the amino acid enriched with the R enantiomer remained in the aqueous solution.In this manner partial resolution of racemic amino acids (Ala, Nva, Phe, Val, Thr) has been carried out with enantiomeric purity 4-50percent. (S)-BPAB or (S)-BPAAPh treatment of a racemic amino acid in the presence of Cu(II) ions (reagents ratio 1:1:1) and CH3O- ions permits enantiomeric enrichment via conversion of the R into S enantiomer (retroracemization).Thus (S)-Ala, (S)-Nva, (S)-Leu, (S)-Val, (S)Phe, and (S)-PhGly of enantiomeric purity 36, 12, 22, 54, 42, and 35percent, respectively, were obtained from racemic samples.CH3O--catalyzed reaction of CuII or CuII with acetaldehyde has given rise to a mixture of diastereomeric complexes, which upon removal of Cu(II) by H2S gave (R)-threonine of 60percent or 97-100percent enantiomeric purity and the threo/allo ratio 6:1 or 19:1, respectively, and permitted recovery of an unchanged initial chiral reagent (S)-BPAB or (S)-BPAAPh.
