Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide
Identifieur interne : 000641 ( Istex/Corpus ); précédent : 000640; suivant : 000642Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide
Auteurs : Christine Hemmerlin ; Manh Thong Cung ; Guy BoussardSource :
- Tetrahedron Letters [ 0040-4039 ] ; 2001.
English descriptors
- KwdEn :
- 2D-NOESY, Amide, Amide function, Aubry, Axial disposition, Azpip, Boussard, Carbonyl, Cdcl3, Cisoid form, Dmso, Elsevier science, Equiv, Hemmerlin, Intramolecular, Intramolecular hydrogen bonds, Isomer, Model rotamer, Nitrogen atom, Peptide, Peptide sequence, Pipecolic acid, Relative populations, Stereoisomer, Tertiary amide function, Tetrahedron, Tetrahedron letters, Torsion angles, X-ray diffraction, azapeptides, beta-turn, conformational studies, hexahydropyridazine 2-carboxylic acid, pipecolic acid.
- Teeft :
- Amide, Amide function, Aubry, Axial disposition, Azpip, Boussard, Carbonyl, Cdcl3, Cisoid form, Dmso, Elsevier science, Equiv, Hemmerlin, Intramolecular, Intramolecular hydrogen bonds, Isomer, Model rotamer, Nitrogen atom, Peptide, Peptide sequence, Pipecolic acid, Relative populations, Stereoisomer, Tertiary amide function, Tetrahedron, Tetrahedron letters, Torsion angles.
Abstract
Abstract: The aza-tripeptide Boc-Ala-AzPip-Ala-NHiPr (AzPip: 2-aza pipecolyl residue) was synthesized in seven steps using preferentially the diisopropylcarbodiimide/1-hydroxy-7-aza-benzotriazole (DIPCDI/AtOH) coupling method and via the Boc-AzPip-OBzl pivotal intermediate. Its crystal molecular structure is characterized by the presence of a βVI-like turn around the N-terminal Ala-AzPip sequence and stabilized by two intramolecular hydrogen bonds sharing the same (Boc)CO carbonyl acceptor. In solution (chloroform, DMSO), two isomers are in equilibrium, one of them resembling the stereoisomer found in the crystal, the other being unfolded, but keeping the cis-isomerism of the Ala-AzPip bond and the pronounced degree of pyramidicity of the axial 2-amide Nα nitrogen atom.
Url:
DOI: 10.1016/S0040-4039(01)00917-0
Links to Exploration step
ISTEX:D9D5047B6A21B2FF04396B8E8BCF3F6352F3139ALe document en format XML
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Boussard</name><affiliation><mods:affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: guy.boussard@ensic.inpl-nancy.fr</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A</idno><date when="2001" year="2001">2001</date><idno type="doi">10.1016/S0040-4039(01)00917-0</idno><idno type="url">https://api.istex.fr/document/D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000641</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000641</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide</title><author><name sortKey="Hemmerlin, Christine" sort="Hemmerlin, Christine" uniqKey="Hemmerlin C" first="Christine" last="Hemmerlin">Christine Hemmerlin</name><affiliation><mods:affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</mods:affiliation></affiliation></author><author><name sortKey="Cung, Manh Thong" sort="Cung, Manh Thong" uniqKey="Cung M" first="Manh Thong" last="Cung">Manh Thong Cung</name><affiliation><mods:affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</mods:affiliation></affiliation></author><author><name sortKey="Boussard, Guy" sort="Boussard, Guy" uniqKey="Boussard G" first="Guy" last="Boussard">Guy Boussard</name><affiliation><mods:affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: guy.boussard@ensic.inpl-nancy.fr</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Tetrahedron Letters</title><title level="j" type="abbrev">TETL</title><idno type="ISSN">0040-4039</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001">2001</date><biblScope unit="volume">42</biblScope><biblScope unit="issue">30</biblScope><biblScope unit="page" from="5009">5009</biblScope><biblScope unit="page" to="5012">5012</biblScope></imprint><idno type="ISSN">0040-4039</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0040-4039</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>2D-NOESY</term><term>Amide</term><term>Amide function</term><term>Aubry</term><term>Axial disposition</term><term>Azpip</term><term>Boussard</term><term>Carbonyl</term><term>Cdcl3</term><term>Cisoid form</term><term>Dmso</term><term>Elsevier science</term><term>Equiv</term><term>Hemmerlin</term><term>Intramolecular</term><term>Intramolecular hydrogen bonds</term><term>Isomer</term><term>Model rotamer</term><term>Nitrogen atom</term><term>Peptide</term><term>Peptide sequence</term><term>Pipecolic acid</term><term>Relative populations</term><term>Stereoisomer</term><term>Tertiary amide function</term><term>Tetrahedron</term><term>Tetrahedron letters</term><term>Torsion angles</term><term>X-ray diffraction</term><term>azapeptides</term><term>beta-turn</term><term>conformational studies</term><term>hexahydropyridazine 2-carboxylic acid</term><term>pipecolic acid</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Amide</term><term>Amide function</term><term>Aubry</term><term>Axial disposition</term><term>Azpip</term><term>Boussard</term><term>Carbonyl</term><term>Cdcl3</term><term>Cisoid form</term><term>Dmso</term><term>Elsevier science</term><term>Equiv</term><term>Hemmerlin</term><term>Intramolecular</term><term>Intramolecular hydrogen bonds</term><term>Isomer</term><term>Model rotamer</term><term>Nitrogen atom</term><term>Peptide</term><term>Peptide sequence</term><term>Pipecolic acid</term><term>Relative populations</term><term>Stereoisomer</term><term>Tertiary amide function</term><term>Tetrahedron</term><term>Tetrahedron letters</term><term>Torsion angles</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The aza-tripeptide Boc-Ala-AzPip-Ala-NHiPr (AzPip: 2-aza pipecolyl residue) was synthesized in seven steps using preferentially the diisopropylcarbodiimide/1-hydroxy-7-aza-benzotriazole (DIPCDI/AtOH) coupling method and via the Boc-AzPip-OBzl pivotal intermediate. Its crystal molecular structure is characterized by the presence of a βVI-like turn around the N-terminal Ala-AzPip sequence and stabilized by two intramolecular hydrogen bonds sharing the same (Boc)CO carbonyl acceptor. In solution (chloroform, DMSO), two isomers are in equilibrium, one of them resembling the stereoisomer found in the crystal, the other being unfolded, but keeping the cis-isomerism of the Ala-AzPip bond and the pronounced degree of pyramidicity of the axial 2-amide Nα nitrogen atom.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>isomer</json:string><json:string>dmso</json:string><json:string>tetrahedron</json:string><json:string>azpip</json:string><json:string>intramolecular</json:string><json:string>stereoisomer</json:string><json:string>cdcl3</json:string><json:string>equiv</json:string><json:string>hemmerlin</json:string><json:string>boussard</json:string><json:string>aubry</json:string><json:string>amide</json:string><json:string>peptide</json:string><json:string>nitrogen atom</json:string><json:string>tetrahedron letters</json:string><json:string>intramolecular hydrogen bonds</json:string><json:string>peptide sequence</json:string><json:string>elsevier science</json:string><json:string>tertiary amide function</json:string><json:string>axial disposition</json:string><json:string>amide function</json:string><json:string>cisoid form</json:string><json:string>pipecolic acid</json:string><json:string>model rotamer</json:string><json:string>torsion angles</json:string><json:string>relative populations</json:string><json:string>carbonyl</json:string></teeft></keywords><author><json:item><name>Christine Hemmerlin</name><affiliations><json:string>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</json:string></affiliations></json:item><json:item><name>Manh Thong Cung</name><affiliations><json:string>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</json:string></affiliations></json:item><json:item><name>Guy Boussard</name><affiliations><json:string>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</json:string><json:string>E-mail: guy.boussard@ensic.inpl-nancy.fr</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>hexahydropyridazine 2-carboxylic acid</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>pipecolic acid</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>azapeptides</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>beta-turn</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>conformational studies</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>X-ray diffraction</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>2D-NOESY</value></json:item></subject><language><json:string>eng</json:string></language><originalGenre><json:string>Short communication</json:string></originalGenre><abstract>The aza-tripeptide Boc-Ala-AzPip-Ala-NHiPr (AzPip: 2-aza pipecolyl residue) was synthesized in seven steps using preferentially the diisopropylcarbodiimide/1-hydroxy-7-aza-benzotriazole (DIPCDI/AtOH) coupling method and via the Boc-AzPip-OBzl pivotal intermediate. Its crystal molecular structure is characterized by the presence of a βVI-like turn around the N-terminal Ala-AzPip sequence and stabilized by two intramolecular hydrogen bonds sharing the same (Boc)CO carbonyl acceptor. In solution (chloroform, DMSO), two isomers are in equilibrium, one of them resembling the stereoisomer found in the crystal, the other being unfolded, but keeping the cis-isomerism of the Ala-AzPip bond and the pronounced degree of pyramidicity of the axial 2-amide Nα nitrogen atom.</abstract><qualityIndicators><score>2.865</score><pdfVersion>1.2</pdfVersion><pdfPageSize>594 x 783 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>7</keywordCount><abstractCharCount>770</abstractCharCount><pdfWordCount>1665</pdfWordCount><pdfCharCount>10553</pdfCharCount><pdfPageCount>4</pdfPageCount><abstractWordCount>100</abstractWordCount></qualityIndicators><title>Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide</title><pii><json:string>S0040-4039(01)00917-0</json:string></pii><genre><json:string>brief-communication</json:string></genre><host><title>Tetrahedron Letters</title><language><json:string>unknown</json:string></language><publicationDate>2001</publicationDate><issn><json:string>0040-4039</json:string></issn><pii><json:string>S0040-4039(00)X2027-8</json:string></pii><volume>42</volume><issue>30</issue><pages><first>5009</first><last>5012</last></pages><genre><json:string>journal</json:string></genre></host><categories><wos><json:string>science</json:string><json:string>chemistry, organic</json:string></wos><scienceMetrix><json:string>natural sciences</json:string><json:string>chemistry</json:string><json:string>organic chemistry</json:string></scienceMetrix><inist><json:string>sciences appliquees, technologies et medecines</json:string><json:string>sciences biologiques et medicales</json:string><json:string>sciences biologiques fondamentales et appliquees. psychologie</json:string></inist></categories><publicationDate>2001</publicationDate><copyrightDate>2001</copyrightDate><doi><json:string>10.1016/S0040-4039(01)00917-0</json:string></doi><id>D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>©2001 Elsevier Science Ltd</p></availability><date>2001</date></publicationStmt><notesStmt><note type="content">Scheme 1: Reagents and conditions: (i) ZCl, TEA, THF; (ii) NaH then Br-(CH2)4-Br, DMF; (iii) HCl/AcOEt (≈3N); (iv) Boc-Ala-OH (1.0 equiv.), diisopropylcarbodiimide (1.0 equiv.), AtOH (1.0 equiv.), DCM; (v) H2, Pd/C 5%, MeOH; (vi) 4-nitrophenylchlorocarbonate, anhydrous AcOEt; (vii) H-Ala-NHiPr (1.5 equiv.), TEA (1.5 equiv.), DMAP (cat.), 80°C, 3 days.</note><note type="content">Figure 1: Stereo drawing of the crystal molecular structure of Boc-l-Ala-(NαS)-AzPip-l-Ala-NHiPr derived from X-ray diffraction.</note><note type="content">Figure 2: Plots of NH̱ proton chemical shifts in the 1H NMR spectrum of isomer M (left) and isomer m (right) as a function of increasing percentages of DMSO-d6 added to the CDCl3 solution (v/v).</note><note type="content">Figure 3: Computer-generated model rotamer of isomer m built on the experimental arrowed NOESY constraints.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide</title><author xml:id="author-0000"><persName><forename type="first">Christine</forename><surname>Hemmerlin</surname></persName><affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Manh Thong</forename><surname>Cung</surname></persName><affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Guy</forename><surname>Boussard</surname></persName><email>guy.boussard@ensic.inpl-nancy.fr</email><note type="correspondence"><p>Corresponding author. Tel.: +33 (0)3 83 17 51 96; fax: +33 (0)3 83 37 99 77</p></note><affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</affiliation></author><idno type="istex">D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A</idno><idno type="DOI">10.1016/S0040-4039(01)00917-0</idno><idno type="PII">S0040-4039(01)00917-0</idno></analytic><monogr><title level="j">Tetrahedron Letters</title><title level="j" type="abbrev">TETL</title><idno type="pISSN">0040-4039</idno><idno type="PII">S0040-4039(00)X2027-8</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001"></date><biblScope unit="volume">42</biblScope><biblScope unit="issue">30</biblScope><biblScope unit="page" from="5009">5009</biblScope><biblScope unit="page" to="5012">5012</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2001</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The aza-tripeptide Boc-Ala-AzPip-Ala-NHiPr (AzPip: 2-aza pipecolyl residue) was synthesized in seven steps using preferentially the diisopropylcarbodiimide/1-hydroxy-7-aza-benzotriazole (DIPCDI/AtOH) coupling method and via the Boc-AzPip-OBzl pivotal intermediate. Its crystal molecular structure is characterized by the presence of a βVI-like turn around the N-terminal Ala-AzPip sequence and stabilized by two intramolecular hydrogen bonds sharing the same (Boc)CO carbonyl acceptor. In solution (chloroform, DMSO), two isomers are in equilibrium, one of them resembling the stereoisomer found in the crystal, the other being unfolded, but keeping the cis-isomerism of the Ala-AzPip bond and the pronounced degree of pyramidicity of the axial 2-amide Nα nitrogen atom.</p></abstract><abstract style="graphical"><p>In crystalline state, the βVI-like folded Boc-Ala-AzPip-Ala-NHiPr (AzPip: 2-aza pipecolic residue) is stabilized by two type 1+3→i and 1+4→i intramolecular hydrogen bonds. The diazaheterocycle adopts a quasi chair conformation and an axial disposition of the 2-N amide function.loc1</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>hexahydropyridazine 2-carboxylic acid</term></item><item><term>pipecolic acid</term></item><item><term>azapeptides</term></item><item><term>beta-turn</term></item><item><term>conformational studies</term></item><item><term>X-ray diffraction</term></item><item><term>2D-NOESY</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2001">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="loc1" NDATA="IMAGE" name="loc1"></istex:entity><istex:entity SYSTEM="sc1" NDATA="IMAGE" name="sc1"></istex:entity><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="sco" xml:lang="en"><item-info><jid>TETL</jid><aid>19427</aid><ce:pii>S0040-4039(01)00917-0</ce:pii><ce:doi>10.1016/S0040-4039(01)00917-0</ce:doi><ce:copyright type="full-transfer" year="2001">Elsevier Science Ltd</ce:copyright></item-info><head><ce:title>Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide</ce:title><ce:author-group><ce:author><ce:given-name>Christine</ce:given-name><ce:surname>Hemmerlin</ce:surname></ce:author><ce:author><ce:given-name>Manh Thong</ce:given-name><ce:surname>Cung</ce:surname></ce:author><ce:author><ce:given-name>Guy</ce:given-name><ce:surname>Boussard</ce:surname><ce:cross-ref refid="COR1">*</ce:cross-ref><ce:e-address type="email">guy.boussard@ensic.inpl-nancy.fr</ce:e-address></ce:author><ce:affiliation><ce:textfn>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel.: +33 (0)3 83 17 51 96; fax: +33 (0)3 83 37 99 77</ce:text></ce:correspondence></ce:author-group><ce:date-received day="23" month="4" year="2001"></ce:date-received><ce:date-accepted day="15" month="5" year="2001"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>The aza-tripeptide Boc-Ala-AzPip-Ala-NH<ce:italic>i</ce:italic>Pr (AzPip: 2-aza pipecolyl residue) was synthesized in seven steps using preferentially the diisopropylcarbodiimide/1-hydroxy-7-aza-benzotriazole (DIPCDI/AtOH) coupling method and via the Boc-AzPip-OBzl pivotal intermediate. Its crystal molecular structure is characterized by the presence of a βVI-like turn around the N-terminal Ala-AzPip sequence and stabilized by two intramolecular hydrogen bonds sharing the same (Boc)CO carbonyl acceptor. In solution (chloroform, DMSO), two isomers are in equilibrium, one of them resembling the stereoisomer found in the crystal, the other being unfolded, but keeping the <ce:italic>cis</ce:italic>-isomerism of the Ala-AzPip bond and the pronounced degree of pyramidicity of the axial 2-amide N<ce:sup>α</ce:sup> nitrogen atom.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:abstract class="graphical"><ce:abstract-sec><ce:simple-para>In crystalline state, the βVI-like folded Boc-Ala-AzPip-Ala-NH<ce:italic>i</ce:italic>Pr (AzPip: 2-aza pipecolic residue) is stabilized by two type 1+3→<ce:italic>i</ce:italic> and 1+4→<ce:italic>i</ce:italic> intramolecular hydrogen bonds. The diazaheterocycle adopts a quasi chair conformation and an axial disposition of the 2-N amide function.</ce:simple-para></ce:abstract-sec><ce:figure><ce:link locator="loc1"></ce:link></ce:figure></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>hexahydropyridazine 2-carboxylic acid</ce:text></ce:keyword><ce:keyword><ce:text>pipecolic acid</ce:text></ce:keyword><ce:keyword><ce:text>azapeptides</ce:text></ce:keyword><ce:keyword><ce:text>beta-turn</ce:text></ce:keyword><ce:keyword><ce:text>conformational studies</ce:text></ce:keyword><ce:keyword><ce:text>X-ray diffraction</ce:text></ce:keyword><ce:keyword><ce:text>2D-NOESY</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide</title></titleInfo><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Hemmerlin</namePart><affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Manh Thong</namePart><namePart type="family">Cung</namePart><affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Guy</namePart><namePart type="family">Boussard</namePart><affiliation>Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568, ENSIC, BP 451, 54001 Nancy, France</affiliation><affiliation>E-mail: guy.boussard@ensic.inpl-nancy.fr</affiliation><description>Corresponding author. Tel.: +33 (0)3 83 17 51 96; fax: +33 (0)3 83 37 99 77</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="brief-communication" displayLabel="Short communication" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-S9SX2MFS-0">brief-communication</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2001</dateIssued><copyrightDate encoding="w3cdtf">2001</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: The aza-tripeptide Boc-Ala-AzPip-Ala-NHiPr (AzPip: 2-aza pipecolyl residue) was synthesized in seven steps using preferentially the diisopropylcarbodiimide/1-hydroxy-7-aza-benzotriazole (DIPCDI/AtOH) coupling method and via the Boc-AzPip-OBzl pivotal intermediate. Its crystal molecular structure is characterized by the presence of a βVI-like turn around the N-terminal Ala-AzPip sequence and stabilized by two intramolecular hydrogen bonds sharing the same (Boc)CO carbonyl acceptor. In solution (chloroform, DMSO), two isomers are in equilibrium, one of them resembling the stereoisomer found in the crystal, the other being unfolded, but keeping the cis-isomerism of the Ala-AzPip bond and the pronounced degree of pyramidicity of the axial 2-amide Nα nitrogen atom.</abstract><abstract type="graphical">In crystalline state, the βVI-like folded Boc-Ala-AzPip-Ala-NHiPr (AzPip: 2-aza pipecolic residue) is stabilized by two type 1+3→i and 1+4→i intramolecular hydrogen bonds. The diazaheterocycle adopts a quasi chair conformation and an axial disposition of the 2-N amide function.loc1 </abstract><note type="content">Scheme 1: Reagents and conditions: (i) ZCl, TEA, THF; (ii) NaH then Br-(CH2)4-Br, DMF; (iii) HCl/AcOEt (≈3N); (iv) Boc-Ala-OH (1.0 equiv.), diisopropylcarbodiimide (1.0 equiv.), AtOH (1.0 equiv.), DCM; (v) H2, Pd/C 5%, MeOH; (vi) 4-nitrophenylchlorocarbonate, anhydrous AcOEt; (vii) H-Ala-NHiPr (1.5 equiv.), TEA (1.5 equiv.), DMAP (cat.), 80°C, 3 days.</note><note type="content">Figure 1: Stereo drawing of the crystal molecular structure of Boc-l-Ala-(NαS)-AzPip-l-Ala-NHiPr derived from X-ray diffraction.</note><note type="content">Figure 2: Plots of NH̱ proton chemical shifts in the 1H NMR spectrum of isomer M (left) and isomer m (right) as a function of increasing percentages of DMSO-d6 added to the CDCl3 solution (v/v).</note><note type="content">Figure 3: Computer-generated model rotamer of isomer m built on the experimental arrowed NOESY constraints.</note><subject lang="en"><genre>Keywords</genre><topic>hexahydropyridazine 2-carboxylic acid</topic><topic>pipecolic acid</topic><topic>azapeptides</topic><topic>beta-turn</topic><topic>conformational studies</topic><topic>X-ray diffraction</topic><topic>2D-NOESY</topic></subject><relatedItem type="host"><titleInfo><title>Tetrahedron Letters</title></titleInfo><titleInfo type="abbreviated"><title>TETL</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">20010723</dateIssued></originInfo><identifier type="ISSN">0040-4039</identifier><identifier type="PII">S0040-4039(00)X2027-8</identifier><part><date>20010723</date><detail type="volume"><number>42</number><caption>vol.</caption></detail><detail type="issue"><number>30</number><caption>no.</caption></detail><extent unit="issue-pages"><start>4943</start><end>5131</end></extent><extent unit="pages"><start>5009</start><end>5012</end></extent></part></relatedItem><identifier type="istex">D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A</identifier><identifier type="ark">ark:/67375/6H6-FFKVLZ02-9</identifier><identifier type="DOI">10.1016/S0040-4039(01)00917-0</identifier><identifier type="PII">S0040-4039(01)00917-0</identifier><accessCondition type="use and reproduction" contentType="copyright">©2001 Elsevier Science Ltd</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Elsevier Science Ltd, ©2001</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/D9D5047B6A21B2FF04396B8E8BCF3F6352F3139A/metadata/json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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