Thyroxine Analogs

MELTZER, ROBERT I.; LUSTGARTEN, DAVID M.; FISCHMAN, ALEX

doi:10.1021/jo01363a010

Cited by 17 publications

(4 citation statements)

References 3 publications

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“…Yield: 59%; IR (film, cm The acrylate was obtained starting from the appropriate 4-hydroxybenzylmalonate in a usual manner. 81 The latter compound was prepared by reduction of 4-hydroxybenzylidenemalonate 82 with NaBH4 (3 equiv) in absolute methanol. Purification on column chromatography using hexane/ethyl acetate (2:1) solution gave the acrylate as brownish oil with 42% of total yield.…”

Section: Methyl 3-[[1-(n-benzyloxycarbonylamino)-3-methylbutyl]hydrox...mentioning

confidence: 99%

The Most Potent Organophosphorus Inhibitors of Leucine Aminopeptidase. Structure-Based Design, Chemistry, and Activity

et al. 2003

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A new class of very potent inhibitors of cytosol leucine aminopeptidase (LAP), a member of the metalloprotease family, is described. The X-ray structure of bovine lens leucine aminopeptidase complexed with the phosphonic acid analogue of leucine (LeuP) was used for structure-based design of novel LAP inhibitors and for the analysis of their interactions with the enzyme binding site. The inhibitors were designed by modification of phosphonic group in the LeuP structure toward finding the substituents bound at the S' side of the enzyme. This resulted in two classes of compounds, the phosphonamidate and phosphinate dipeptide analogues, which were synthesized and evaluated as inhibitors of the enzyme. The in vitro kinetic studies for the phosphinate dipeptide analogues revealed that these compounds belong to the group of the most effective LAP inhibitors found so far. Their further modification at the P1 position resulted in more active inhibitors, hPheP[CH(2)]Phe and hPheP[CH(2)]Tyr (K(i) values 66 nM and 67 nM, respectively, for the mixture of four diastereomers). The binding affinities of these inhibitors toward the enzyme are the highest, if considering all compounds containing a phosphorus atom that mimic the transition state of the reaction catalyzed by LAP. To evaluate selectivity of the designed LAP inhibitors, additional tests toward aminopeptidase N (APN) were performed. The key feature, which determines their selectivity, is structure at the P1' position. Aromatic and aliphatic substituents placed at this position strongly interact with the LAP S1' binding pocket, while a significant increase in binding affinity toward APN was observed for compounds containing aromatic versus leucine side chains at the P1' position. The most selective inhibitor, hPheP[CH(2)]Leu, binds to LAP with 15 times higher affinity than to APN. One of the studied compounds, hPheP[CH(2)]Tyr, appeared to be very potent inhibitor of APN (K(i) = 36 nM for the mixture of four diastereomers). The most promising LAP inhibitors designed by computer-aided approach, the phosphonamidate dipeptide analogues, were unstable at pH below 12, because of the P-N bond decomposition, which excluded the possibility of determination of their binding affinities toward LAP.

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Section: Methyl 3-[[1-(n-benzyloxycarbonylamino)-3-methylbutyl]hydrox...mentioning

confidence: 99%

The Most Potent Organophosphorus Inhibitors of Leucine Aminopeptidase. Structure-Based Design, Chemistry, and Activity

et al. 2003

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“…The Knoevenagel condensation, discovered by E. Knoevenagel in 1896, is widely used both in the academic environment and in the chemical–pharmaceutical and perfume industries. In general, a secondary amine catalyzes the Knoevenagel condensation in the presence of a small amount of an acid such as acetic acid and benzoic acid (commercially available benzaldehyde contains a small amount of benzoic acid), and the reaction can occur through an iminium or aminal (Knoevenagel mechanism, Scheme , reaction 1) and/or an ammonium enolate (Hann–Lapworth mechanism) . When a pure aldehyde is employed, a small amount of an acid additive should be added .…”

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confidence: 99%

Organocatalytic Knoevenagel Condensations by Means of Carbamic Acid Ammonium Salts

Mase

Horibe

2013

Org. Lett.

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The Knoevenagel condensation between an active methylene compound and an aromatic aldehyde with a carbamic acid ammonium salt used as an organocatalyst gave the desired Knoevenagel products in up to 98% yield. The reaction occurred at rt and in a short reaction time under solvent-free conditions. In addition, no extraction, wash, or chromatography steps were needed to obtain a high-purity Knoevenagel product.

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“…For the Knoevenagel reaction, according to the homogeneous catalyzed mechanism and some reported heterogeneous systems, we have proposed the heterogeneous catalytic mechanism in this work. The SBA‐15‐Aep catalyst shows obvious acidic‐basic synergies which the SBA‐15‐Q not.…”

Section: Resultsmentioning

confidence: 99%

Asymmetric Knoevenagel‐Phospha‐Michael Tandem Reaction Synergistically Catalyzed by Achiral Silanols and Grafted Chiral Amines on Mesoporous Silica

Yan

Jiang

et al. 2019

Asian J Org Chem

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Highly efficient and enantioselective asymmetric Knoevenagel-phospha-Michael tandem reactions have been achieved on bifunctional heterogeneous catalysts with inherent silanols as acidic sites and immobilized chiral amines as basic sites. Final products were afforded in yields of up to 99% and ee values of up to 99%. The effects of substituents on benzaldehyde and molecular dimensions of phosphites have also been investigated. Larger substrates can access the catalytic site inside larger mesoporous pores, thereby improving both of yield and ee of final products.

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Thyroxine Analogs

Cited by 17 publications

References 3 publications

The Most Potent Organophosphorus Inhibitors of Leucine Aminopeptidase. Structure-Based Design, Chemistry, and Activity

The Most Potent Organophosphorus Inhibitors of Leucine Aminopeptidase. Structure-Based Design, Chemistry, and Activity

Organocatalytic Knoevenagel Condensations by Means of Carbamic Acid Ammonium Salts

Asymmetric Knoevenagel‐Phospha‐Michael Tandem Reaction Synergistically Catalyzed by Achiral Silanols and Grafted Chiral Amines on Mesoporous Silica

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