The CERT antagonist HPA-12: First practical synthesis and individual binding evaluation of the four stereoisomers

Santos, Cécile; Fleury, Laurence; Rodriguez, Frédéric; Markus, Jozef; Berkeš, Dušan; Daı̈ch, Adam; Ausseil, Frédéric; Baudoin-Dehoux, Cécile; Ballereau, Stéphanie; Génisson, Yves

doi:10.1016/j.bmc.2015.03.019

Cited by 20 publications

(28 citation statements)

References 36 publications

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“…[21] The lactone 24 was then reduced under standard conditions to give aminobutanediol 25.H ydrogenolysis of the 1-phenylethyl group followed by as elective N-acylation of amino alcohol 26 furnished (1R,3S)-HPA-12. [21] The lactone 24 was then reduced under standard conditions to give aminobutanediol 25.H ydrogenolysis of the 1-phenylethyl group followed by as elective N-acylation of amino alcohol 26 furnished (1R,3S)-HPA-12.…”

Section: Syntheses Of Hpa-12mentioning

confidence: 99%

“…[21] Following our revisiono ft he configuration of HPA-12 [12a] and its subsequent confirmation by Kobayashi's group, [12b] the Scheme6.Gram-scale synthesis of (1R,3S)-HPA-12byK obayashi: [12b] a) ZnF 2 (10 mol %), Ligand (10 mol %), CTAB (2 mol %), H 2 O, 0 8C, 80 %( 81 % ee); b) i) C 11 H 23 COCl, NEt 3 ,CH 2 Cl 2 ,08C, 87 %; ii)NaBH 4 , syn:45% and anti:5 0%; iii)SmI 2 ,THF/MeOH,08C, 87 %. [21] Following our revisiono ft he configuration of HPA-12 [12a] and its subsequent confirmation by Kobayashi's group, [12b] the Scheme6.Gram-scale synthesis of (1R,3S)-HPA-12byK obayashi: [12b] a) ZnF 2 (10 mol %), Ligand (10 mol %), CTAB (2 mol %), H 2 O, 0 8C, 80 %( 81 % ee); b) i) C 11 H 23 COCl, NEt 3 ,CH 2 Cl 2 ,08C, 87 %; ii)NaBH 4 , syn:45% and anti:5 0%; iii)SmI 2 ,THF/MeOH,08C, 87 %.…”

Section: Syntheses Of Hpa-12mentioning

confidence: 99%

“…[34] An acyl chain comprised between C11a nd C15 led to comparable inhibitory potency in ac ell-based assay,w hilet he presence of shorter or longer alkanamidef ragments either diminished or suppressed the activity. [21] AT R-FRET homogeneousphase assay was specifically developed, allowing complete determination of HPA-12 EC 50 . [34] We reported the first unified asymmetric synthesis and individual binding evaluation of all four HPA-12 stereoisomers with the CERT START domain.…”

Section: Syntheses Of Hpas Analogues and Structure-activity Relationsmentioning

confidence: 99%

“…Crystals tructures of as eries of (1R,3R)-HPAs with C13 to C16 acyl chains in complex with the CERT START domain were reported,i ndicating ar ecognition mode very similart ot hat of the naturalc argo lipid Cer. [21,35] Arenz and co-workers described n-a nd tert-butyld erivatives that showed as trongly reduced binding to the CERT protein in an in vitro fluorescent intensity assay.…”

Section: Syntheses Of Hpas Analogues and Structure-activity Relationsmentioning

confidence: 99%

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Chemistry and Biology of HPAs: A Family of Ceramide Trafficking Inhibitors

Berkeš¹,

Daı̈ch

Santos

et al. 2016

Chemistry A European J

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In 2001, two years before the disclosure of the CERT-associated Cer transfer machinery, N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)alkanamides (HPAs) were described as the first, and to date unique, family of intracellular Cer trafficking inhibitors. The dodecanamide derivative, HPA-12, turned out to be a benchmark as a cellular inhibitor of CERT-mediated de novo sphingomyelin biosynthesis. In only 15 years after its first disclosure, this compound has prompted a growing number of biological and chemical studies. Its initial chemical development closely paralleled the study of the CERT protein. It was only after its structural revision in 2011 that HPA-12 received broad attention from the synthetic chemistry community, leading to novel analogues with enhanced protein binding. This Minireview aims at presenting an exhaustive report of the syntheses of HPA-12 and analogues. Biological activities of this CERT inhibitor and structure-activity relationships are also presented to afford a comprehensive overview of the chemistry and biology of the HPA series.

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Section: Syntheses Of Hpa-12mentioning

confidence: 99%

Section: Syntheses Of Hpa-12mentioning

confidence: 99%

Section: Syntheses Of Hpas Analogues and Structure-activity Relationsmentioning

confidence: 99%

Section: Syntheses Of Hpas Analogues and Structure-activity Relationsmentioning

confidence: 99%

See 2 more Smart Citations

Chemistry and Biology of HPAs: A Family of Ceramide Trafficking Inhibitors

Berkeš¹,

Daı̈ch

Santos

et al. 2016

Chemistry A European J

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“…Very recently, Delgado et al reported a straightforward synthesis of HPA-12 from D-aspartic acid, 15 while Genisson et al have used crystallization inducedasymmetric transformation technology for the multi-gram scale synthesis of HPA 12 and its isomers 16. …”

mentioning

confidence: 99%

Chelation controlled reduction of N-protected β-amino ketones toward the synthesis of HPA-12 and analogues

Chacko¹,

Kalita²,

Ramapanicker³

2015

Tetrahedron: Asymmetry

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State of the Art in Crystallization‐Induced Diastereomer Transformations

Kolarovič

Jakubec

2021

Adv Synth Catal

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Crystallization-induced diastereomer transformations (CIDT) enable isolation of the target compounds in high enantio-and diastereomeric purities and with up to quantitative yields simply by filtration. Numerous inspiring examples of this appealing synthetic strategy reported over the last fifteen years are reviewed. Important observations along with aspects to consider when designing CIDT experiments are discussed. 3.3. Formation of Schiff Base or Related Intermediates 3.4. Aza-Michael and Mannich-Type Reactions 3.5. Strecker Reaction 3.6. Aldol Reactions 3.7. Epimerization at Phosphorus-Based Stereocenters 3.8. Racemization/Epimerization through Change of Conformation 3.9. Miscellaneous Examples of CIDT 4.Conclusions and Perspectives

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The CERT antagonist HPA-12: First practical synthesis and individual binding evaluation of the four stereoisomers

Cited by 20 publications

References 36 publications

Chemistry and Biology of HPAs: A Family of Ceramide Trafficking Inhibitors

Chemistry and Biology of HPAs: A Family of Ceramide Trafficking Inhibitors

Chelation controlled reduction of N-protected β-amino ketones toward the synthesis of HPA-12 and analogues

State of the Art in Crystallization‐Induced Diastereomer Transformations

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