Peptide Enolates. C‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides via dilithium azadienediolates
Identifieur interne : 000D94 ( Istex/Corpus ); précédent : 000D93; suivant : 000D95Peptide Enolates. C‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides via dilithium azadienediolates
Auteurs : Hans G. Bossler ; Dieter SeebachSource :
- Helvetica Chimica Acta [ 0018-019X ] ; 1994-06-29.
English descriptors
- KwdEn :
- Acoet, Acta, Alkylation, Alkylations, Amino acids, Angew, Benzyl, Benzyl bromide, Bromide, Bromoacetate, Buli, Bzlbr, Cdc1, Cdci, Chem, Chimica, Chloroformate, Conformation, Derivative, Dropwise, Electrophiles, Enolate, Enolates, Esterification, Etoh, Glycine, Helv, Helvetica, Helvetica chimica acta, Ibid, Isobutyl, Isobutyl chloroformate, Lett, Libr, Ltmp, Meabu, Meleu, Mgso, Mmol, Moiety, Nacl, Obzl, Pentapeptide, Peptide, Quant, Sarcosine, Seebach, Soln, Tetrahedron, Tetrahedron lett, Tripeptide, Workup.
- Teeft :
- Acoet, Acta, Alkylation, Alkylations, Amino acids, Angew, Benzyl, Benzyl bromide, Bromide, Bromoacetate, Buli, Bzlbr, Cdc1, Cdci, Chem, Chimica, Chloroformate, Conformation, Derivative, Dropwise, Electrophiles, Enolate, Enolates, Esterification, Etoh, Glycine, Helv, Helvetica, Helvetica chimica acta, Ibid, Isobutyl, Isobutyl chloroformate, Lett, Libr, Ltmp, Meabu, Meleu, Mgso, Mmol, Moiety, Nacl, Obzl, Pentapeptide, Peptide, Quant, Sarcosine, Seebach, Soln, Tetrahedron, Tetrahedron lett, Tripeptide, Workup.
Abstract
The Boc‐protected tripeptides Boc‐Val‐Gly‐Leu‐OH (1), Boc‐Leu‐Sar‐Leu‐OH (2), Boc‐Leu‐Gly‐MeLeu‐OH (3), and Boc‐Val‐BzlGly‐Leu‐OMe (64), tetrapeptide Boc‐Leu‐Gly‐Pro‐Leu‐OH (9), and pentapeptides Boc‐Val‐Leu‐Gly‐Abu‐Ile‐OH (4), Boc‐Val‐Leu‐Sar‐MeAbu‐Ile‐OH (5), Boc‐Val‐Leu‐Gly‐MeAbu‐Ile‐OH (6), Boc‐Val‐Leu‐BzlGly‐BzlAbu‐Ile‐OH (7), and Boc‐Val‐Leu‐Gly‐BzlAbu‐Ile‐OH (8) are prepared by conventional methods (Schemes 4–7) or by direct benzylation of the corresponding precursors (Scheme 8). Polylithiations in THF give up to Li6 derivatives containing glycine, sarcosine or N‐benzylglycine Li enolate moieties (A–H). The polylithiated systems with a dilithium azadienediolate unit (C, F–H) are best generated by treatment with t‐BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (R)‐configuration (i.e. a D‐amino‐acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i‐PrI, allyl and benzyl bromide, ethyl bromoacetate, CO2, and Me2S2 (Schemes 11–13). No epimerizations of the starting materials (racemization of the amino‐acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock‐freezing or by very slow cooling from room temperature to −75° before lithiation, give rise to different stereoselectivities (Scheme 11). The latter and the yields can also be influenced by tempering the lithiated species before (Scheme 9) or after addition of the electrophiles (Scheme 12). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80–95%). The results described are yet another demonstration that peptides may be backbone‐modified through Li enolates, and that whole series of analogous peptide derivatives with various side chains may thus be produced from a given precursor.
Url:
DOI: 10.1002/hlca.19940770424
Links to Exploration step
ISTEX:AEE629B8C71271B54327612E7962EFC1D9170AE9Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Peptide Enolates. C‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides via dilithium azadienediolates</title><author><name sortKey="Bossler, Hans G" sort="Bossler, Hans G" uniqKey="Bossler H" first="Hans G." last="Bossler">Hans G. Bossler</name><affiliation><mods:affiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</mods:affiliation></affiliation></author><author><name sortKey="Seebach, Dieter" sort="Seebach, Dieter" uniqKey="Seebach D" first="Dieter" last="Seebach">Dieter Seebach</name><affiliation><mods:affiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:AEE629B8C71271B54327612E7962EFC1D9170AE9</idno><date when="1994" year="1994">1994</date><idno type="doi">10.1002/hlca.19940770424</idno><idno type="url">https://api.istex.fr/document/AEE629B8C71271B54327612E7962EFC1D9170AE9/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000D94</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000D94</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Peptide Enolates. <hi rend="italic">C</hi>‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides <hi rend="italic">via</hi> dilithium azadienediolates</title><author><name sortKey="Bossler, Hans G" sort="Bossler, Hans G" uniqKey="Bossler H" first="Hans G." last="Bossler">Hans G. Bossler</name><affiliation><mods:affiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</mods:affiliation></affiliation></author><author><name sortKey="Seebach, Dieter" sort="Seebach, Dieter" uniqKey="Seebach D" first="Dieter" last="Seebach">Dieter Seebach</name><affiliation><mods:affiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Helvetica Chimica Acta</title><title level="j" type="alt">HELVETICA CHIMICA ACTA</title><idno type="ISSN">0018-019X</idno><idno type="eISSN">1522-2675</idno><imprint><biblScope unit="vol">77</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="1124">1124</biblScope><biblScope unit="page" to="1165">1165</biblScope><biblScope unit="page-count">42</biblScope><publisher>WILEY‐VCH Verlag GmbH</publisher><pubPlace>Weinheim</pubPlace><date type="published" when="1994-06-29">1994-06-29</date></imprint><idno type="ISSN">0018-019X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0018-019X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acoet</term><term>Acta</term><term>Alkylation</term><term>Alkylations</term><term>Amino acids</term><term>Angew</term><term>Benzyl</term><term>Benzyl bromide</term><term>Bromide</term><term>Bromoacetate</term><term>Buli</term><term>Bzlbr</term><term>Cdc1</term><term>Cdci</term><term>Chem</term><term>Chimica</term><term>Chloroformate</term><term>Conformation</term><term>Derivative</term><term>Dropwise</term><term>Electrophiles</term><term>Enolate</term><term>Enolates</term><term>Esterification</term><term>Etoh</term><term>Glycine</term><term>Helv</term><term>Helvetica</term><term>Helvetica chimica acta</term><term>Ibid</term><term>Isobutyl</term><term>Isobutyl chloroformate</term><term>Lett</term><term>Libr</term><term>Ltmp</term><term>Meabu</term><term>Meleu</term><term>Mgso</term><term>Mmol</term><term>Moiety</term><term>Nacl</term><term>Obzl</term><term>Pentapeptide</term><term>Peptide</term><term>Quant</term><term>Sarcosine</term><term>Seebach</term><term>Soln</term><term>Tetrahedron</term><term>Tetrahedron lett</term><term>Tripeptide</term><term>Workup</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Acoet</term><term>Acta</term><term>Alkylation</term><term>Alkylations</term><term>Amino acids</term><term>Angew</term><term>Benzyl</term><term>Benzyl bromide</term><term>Bromide</term><term>Bromoacetate</term><term>Buli</term><term>Bzlbr</term><term>Cdc1</term><term>Cdci</term><term>Chem</term><term>Chimica</term><term>Chloroformate</term><term>Conformation</term><term>Derivative</term><term>Dropwise</term><term>Electrophiles</term><term>Enolate</term><term>Enolates</term><term>Esterification</term><term>Etoh</term><term>Glycine</term><term>Helv</term><term>Helvetica</term><term>Helvetica chimica acta</term><term>Ibid</term><term>Isobutyl</term><term>Isobutyl chloroformate</term><term>Lett</term><term>Libr</term><term>Ltmp</term><term>Meabu</term><term>Meleu</term><term>Mgso</term><term>Mmol</term><term>Moiety</term><term>Nacl</term><term>Obzl</term><term>Pentapeptide</term><term>Peptide</term><term>Quant</term><term>Sarcosine</term><term>Seebach</term><term>Soln</term><term>Tetrahedron</term><term>Tetrahedron lett</term><term>Tripeptide</term><term>Workup</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">The Boc‐protected tripeptides Boc‐Val‐Gly‐Leu‐OH (1), Boc‐Leu‐Sar‐Leu‐OH (2), Boc‐Leu‐Gly‐MeLeu‐OH (3), and Boc‐Val‐BzlGly‐Leu‐OMe (64), tetrapeptide Boc‐Leu‐Gly‐Pro‐Leu‐OH (9), and pentapeptides Boc‐Val‐Leu‐Gly‐Abu‐Ile‐OH (4), Boc‐Val‐Leu‐Sar‐MeAbu‐Ile‐OH (5), Boc‐Val‐Leu‐Gly‐MeAbu‐Ile‐OH (6), Boc‐Val‐Leu‐BzlGly‐BzlAbu‐Ile‐OH (7), and Boc‐Val‐Leu‐Gly‐BzlAbu‐Ile‐OH (8) are prepared by conventional methods (Schemes 4–7) or by direct benzylation of the corresponding precursors (Scheme 8). Polylithiations in THF give up to Li6 derivatives containing glycine, sarcosine or N‐benzylglycine Li enolate moieties (A–H). The polylithiated systems with a dilithium azadienediolate unit (C, F–H) are best generated by treatment with t‐BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (R)‐configuration (i.e. a D‐amino‐acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i‐PrI, allyl and benzyl bromide, ethyl bromoacetate, CO2, and Me2S2 (Schemes 11–13). No epimerizations of the starting materials (racemization of the amino‐acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock‐freezing or by very slow cooling from room temperature to −75° before lithiation, give rise to different stereoselectivities (Scheme 11). The latter and the yields can also be influenced by tempering the lithiated species before (Scheme 9) or after addition of the electrophiles (Scheme 12). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80–95%). The results described are yet another demonstration that peptides may be backbone‐modified through Li enolates, and that whole series of analogous peptide derivatives with various side chains may thus be produced from a given precursor.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>mmol</json:string><json:string>cdci</json:string><json:string>etoh</json:string><json:string>libr</json:string><json:string>acta</json:string><json:string>chimica</json:string><json:string>quant</json:string><json:string>obzl</json:string><json:string>helvetica</json:string><json:string>peptide</json:string><json:string>soln</json:string><json:string>chem</json:string><json:string>helvetica chimica acta</json:string><json:string>benzyl</json:string><json:string>seebach</json:string><json:string>chloroformate</json:string><json:string>bromide</json:string><json:string>isobutyl</json:string><json:string>meabu</json:string><json:string>buli</json:string><json:string>isobutyl chloroformate</json:string><json:string>glycine</json:string><json:string>tetrahedron</json:string><json:string>cdc1</json:string><json:string>electrophiles</json:string><json:string>sarcosine</json:string><json:string>nacl</json:string><json:string>enolate</json:string><json:string>workup</json:string><json:string>angew</json:string><json:string>benzyl bromide</json:string><json:string>lett</json:string><json:string>derivative</json:string><json:string>pentapeptide</json:string><json:string>ibid</json:string><json:string>mgso</json:string><json:string>enolates</json:string><json:string>amino acids</json:string><json:string>tetrahedron lett</json:string><json:string>tripeptide</json:string><json:string>bromoacetate</json:string><json:string>bzlbr</json:string><json:string>ltmp</json:string><json:string>acoet</json:string><json:string>moiety</json:string><json:string>meleu</json:string><json:string>conformation</json:string><json:string>esterification</json:string><json:string>alkylation</json:string><json:string>dropwise</json:string><json:string>alkylations</json:string><json:string>helv</json:string><json:string>general procedure</json:string><json:string>ethyl bromoacetate</json:string><json:string>helvetica chimica</json:string><json:string>chromatographic purification</json:string><json:string>crude product</json:string><json:string>amino</json:string></teeft></keywords><author><json:item><name>Hans G. Bossler</name><affiliations><json:string>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</json:string></affiliations></json:item><json:item><name>Dieter Seebach</name><affiliations><json:string>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</json:string><json:string>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</json:string></affiliations></json:item></author><articleId><json:string>HLCA19940770424</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>The Boc‐protected tripeptides Boc‐Val‐Gly‐Leu‐OH (1), Boc‐Leu‐Sar‐Leu‐OH (2), Boc‐Leu‐Gly‐MeLeu‐OH (3), and Boc‐Val‐BzlGly‐Leu‐OMe (64), tetrapeptide Boc‐Leu‐Gly‐Pro‐Leu‐OH (9), and pentapeptides Boc‐Val‐Leu‐Gly‐Abu‐Ile‐OH (4), Boc‐Val‐Leu‐Sar‐MeAbu‐Ile‐OH (5), Boc‐Val‐Leu‐Gly‐MeAbu‐Ile‐OH (6), Boc‐Val‐Leu‐BzlGly‐BzlAbu‐Ile‐OH (7), and Boc‐Val‐Leu‐Gly‐BzlAbu‐Ile‐OH (8) are prepared by conventional methods (Schemes 4–7) or by direct benzylation of the corresponding precursors (Scheme 8). Polylithiations in THF give up to Li6 derivatives containing glycine, sarcosine or N‐benzylglycine Li enolate moieties (A–H). The polylithiated systems with a dilithium azadienediolate unit (C, F–H) are best generated by treatment with t‐BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (R)‐configuration (i.e. a D‐amino‐acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i‐PrI, allyl and benzyl bromide, ethyl bromoacetate, CO2, and Me2S2 (Schemes 11–13). No epimerizations of the starting materials (racemization of the amino‐acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock‐freezing or by very slow cooling from room temperature to −75° before lithiation, give rise to different stereoselectivities (Scheme 11). The latter and the yields can also be influenced by tempering the lithiated species before (Scheme 9) or after addition of the electrophiles (Scheme 12). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80–95%). The results described are yet another demonstration that peptides may be backbone‐modified through Li enolates, and that whole series of analogous peptide derivatives with various side chains may thus be produced from a given precursor.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>486 x 684 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>2061</abstractCharCount><pdfWordCount>30493</pdfWordCount><pdfCharCount>157777</pdfCharCount><pdfPageCount>42</pdfPageCount><abstractWordCount>267</abstractWordCount></qualityIndicators><title>Peptide Enolates. C‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides via dilithium azadienediolates</title><genre><json:string>article</json:string></genre><host><title>Helvetica Chimica Acta</title><language><json:string>unknown</json:string></language><doi><json:string>10.1002/(ISSN)1522-2675</json:string></doi><issn><json:string>0018-019X</json:string></issn><eissn><json:string>1522-2675</json:string></eissn><publisherId><json:string>HLCA</json:string></publisherId><volume>77</volume><issue>4</issue><pages><first>1124</first><last>1165</last><total>42</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Article</value></json:item></subject></host><categories><wos><json:string>science</json:string><json:string>chemistry, multidisciplinary</json:string></wos><scienceMetrix><json:string>natural sciences</json:string><json:string>chemistry</json:string><json:string>general chemistry</json:string></scienceMetrix></categories><publicationDate>1994</publicationDate><copyrightDate>1994</copyrightDate><doi><json:string>10.1002/hlca.19940770424</json:string></doi><id>AEE629B8C71271B54327612E7962EFC1D9170AE9</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/AEE629B8C71271B54327612E7962EFC1D9170AE9/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/AEE629B8C71271B54327612E7962EFC1D9170AE9/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/AEE629B8C71271B54327612E7962EFC1D9170AE9/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Peptide Enolates. <hi rend="italic">C</hi>‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides <hi rend="italic">via</hi> dilithium azadienediolates</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>WILEY‐VCH Verlag GmbH</publisher><pubPlace>Weinheim</pubPlace><availability><licence>Copyright © 1994 Verlag GmbH & Co. KGaA, Weinheim</licence></availability><date type="published" when="1994-06-29"></date></publicationStmt><notesStmt><note type="content-type" subtype="article" source="article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</note><note type="publication-type" subtype="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="article"><analytic><title level="a" type="main" xml:lang="en">Peptide Enolates. <hi rend="italic">C</hi>‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides <hi rend="italic">via</hi> dilithium azadienediolates</title><author xml:id="author-0000"><persName><forename type="first">Hans G.</forename><surname>Bossler</surname></persName><affiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich<address><country key="CH"></country></address></affiliation><note type="foot">Part of the Ph.D. thesis of H. G. B., Dissertation No. 10254, ETH‐Zürich, 1993</note></author><author xml:id="author-0001" role="corresp"><persName><forename type="first">Dieter</forename><surname>Seebach</surname></persName><affiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich<address><country key="CH"></country></address></affiliation><affiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</affiliation></author><idno type="istex">AEE629B8C71271B54327612E7962EFC1D9170AE9</idno><idno type="ark">ark:/67375/WNG-RX12B67H-K</idno><idno type="DOI">10.1002/hlca.19940770424</idno><idno type="unit">HLCA19940770424</idno><idno type="toTypesetVersion">file:HLCA.HLCA19940770424.pdf</idno></analytic><monogr><title level="j" type="main">Helvetica Chimica Acta</title><title level="j" type="alt">HELVETICA CHIMICA ACTA</title><idno type="pISSN">0018-019X</idno><idno type="eISSN">1522-2675</idno><idno type="book-DOI">10.1002/(ISSN)1522-2675</idno><idno type="book-part-DOI">10.1002/hlca.v77:4</idno><idno type="product">HLCA</idno><imprint><biblScope unit="vol">77</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="1124">1124</biblScope><biblScope unit="page" to="1165">1165</biblScope><biblScope unit="page-count">42</biblScope><publisher>WILEY‐VCH Verlag GmbH</publisher><pubPlace>Weinheim</pubPlace><date type="published" when="1994-06-29"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>The Boc‐protected tripeptides Boc‐Val‐Gly‐Leu‐OH (<hi rend="bold">1</hi>), Boc‐Leu‐Sar‐Leu‐OH (<hi rend="bold">2</hi>), Boc‐Leu‐Gly‐MeLeu‐OH (<hi rend="bold">3</hi>), and Boc‐Val‐BzlGly‐Leu‐OMe (<hi rend="bold">64</hi>), tetrapeptide Boc‐Leu‐Gly‐Pro‐Leu‐OH (<hi rend="bold">9</hi>), and pentapeptides Boc‐Val‐Leu‐Gly‐Abu‐Ile‐OH (<hi rend="bold">4</hi>), Boc‐Val‐Leu‐Sar‐MeAbu‐Ile‐OH (<hi rend="bold">5</hi>), Boc‐Val‐Leu‐Gly‐MeAbu‐Ile‐OH (<hi rend="bold">6</hi>), Boc‐Val‐Leu‐BzlGly‐BzlAbu‐Ile‐OH (<hi rend="bold">7</hi>), and Boc‐Val‐Leu‐Gly‐BzlAbu‐Ile‐OH (<hi rend="bold">8</hi>) are prepared by conventional methods (<hi rend="italic">Schemes 4–7</hi>) or by direct benzylation of the corresponding precursors (<hi rend="italic">Scheme 8</hi>). Polylithiations in THF give up to Li<hi rend="subscript">6</hi> derivatives containing glycine, sarcosine or <hi rend="italic">N</hi>‐benzylglycine Li enolate moieties (<hi rend="bold">A–H</hi>). The polylithiated systems with a dilithium azadienediolate unit (<hi rend="bold">C, F–H</hi>) are best generated by treatment with <hi rend="italic">t</hi>‐BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (<hi rend="italic">R</hi>)‐configuration (<hi rend="italic">i.e.</hi> a <hi rend="smallCaps">D</hi>‐amino‐acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i‐PrI, allyl and benzyl bromide, ethyl bromoacetate, CO<hi rend="subscript">2</hi>, and Me<hi rend="subscript">2</hi>S<hi rend="subscript">2</hi> (<hi rend="italic">Schemes 11–13</hi>). No epimerizations of the starting materials (racemization of the amino‐acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock‐freezing or by very slow cooling from room temperature to −75° before lithiation, give rise to different stereoselectivities (<hi rend="italic">Scheme 11</hi>). The latter and the yields can also be influenced by tempering the lithiated species before (<hi rend="italic">Scheme 9</hi>) or after addition of the electrophiles (<hi rend="italic">Scheme 12</hi>). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80–95%). The results described are yet another demonstration that peptides may be backbone‐modified through Li enolates, and that whole series of analogous peptide derivatives with various side chains may thus be produced from a given precursor.</p></abstract><textClass><keywords rend="articleCategory"><term>Article</term></keywords><keywords rend="tocHeading1"><term>Articles</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/AEE629B8C71271B54327612E7962EFC1D9170AE9/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>WILEY‐VCH Verlag GmbH</publisherName><publisherLoc>Weinheim</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1522-2675</doi><issn type="print">0018-019X</issn><issn type="electronic">1522-2675</issn><idGroup><id type="product" value="HLCA"></id></idGroup><titleGroup><title type="main" xml:lang="de" sort="HELVETICA CHIMICA ACTA">Helvetica Chimica Acta</title><title type="short">HCA</title></titleGroup></publicationMeta><publicationMeta level="part" position="40"><doi origin="wiley" registered="yes">10.1002/hlca.v77:4</doi><numberingGroup><numbering type="journalVolume" number="77">77</numbering><numbering type="journalIssue">4</numbering></numberingGroup><coverDate startDate="1994-06-29">29 June 1994</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="24" status="forIssue"><doi origin="wiley" registered="yes">10.1002/hlca.19940770424</doi><idGroup><id type="unit" value="HLCA19940770424"></id></idGroup><countGroup><count type="pageTotal" number="42"></count></countGroup><titleGroup><title type="articleCategory">Article</title><title type="tocHeading1">Articles</title></titleGroup><copyright ownership="publisher">Copyright © 1994 Verlag GmbH & Co. KGaA, Weinheim</copyright><eventGroup><event type="firstOnline" date="2004-10-25"></event><event type="publishedOnlineFinalForm" date="2004-10-25"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:HeaderRef result:HeaderRef" date="2010-03-05"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-27"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-24"></event></eventGroup><numberingGroup><numbering type="pageFirst">1124</numbering><numbering type="pageLast">1165</numbering></numberingGroup><correspondenceTo>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:HLCA.HLCA19940770424.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="0"></count><count type="referenceTotal" number="57"></count></countGroup><titleGroup><title type="main" xml:lang="en">Peptide Enolates. <i>C</i>‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides <i>via</i> dilithium azadienediolates</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" noteRef="#fn1"><personName><givenNames>Hans G.</givenNames><familyName>Bossler</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Dieter</givenNames><familyName>Seebach</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="CH" type="organization"><unparsedAffiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The Boc‐protected tripeptides Boc‐Val‐Gly‐Leu‐OH (<b>1</b>), Boc‐Leu‐Sar‐Leu‐OH (<b>2</b>), Boc‐Leu‐Gly‐MeLeu‐OH (<b>3</b>), and Boc‐Val‐BzlGly‐Leu‐OMe (<b>64</b>), tetrapeptide Boc‐Leu‐Gly‐Pro‐Leu‐OH (<b>9</b>), and pentapeptides Boc‐Val‐Leu‐Gly‐Abu‐Ile‐OH (<b>4</b>), Boc‐Val‐Leu‐Sar‐MeAbu‐Ile‐OH (<b>5</b>), Boc‐Val‐Leu‐Gly‐MeAbu‐Ile‐OH (<b>6</b>), Boc‐Val‐Leu‐BzlGly‐BzlAbu‐Ile‐OH (<b>7</b>), and Boc‐Val‐Leu‐Gly‐BzlAbu‐Ile‐OH (<b>8</b>) are prepared by conventional methods (<i>Schemes 4–7</i>) or by direct benzylation of the corresponding precursors (<i>Scheme 8</i>). Polylithiations in THF give up to Li<sub>6</sub> derivatives containing glycine, sarcosine or <i>N</i>‐benzylglycine Li enolate moieties (<b>A–H</b>). The polylithiated systems with a dilithium azadienediolate unit (<b>C, F–H</b>) are best generated by treatment with <i>t</i>‐BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (<i>R</i>)‐configuration (<i>i.e.</i> a <sc>D</sc>‐amino‐acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i‐PrI, allyl and benzyl bromide, ethyl bromoacetate, CO<sub>2</sub>, and Me<sub>2</sub>S<sub>2</sub> (<i>Schemes 11–13</i>). No epimerizations of the starting materials (racemization of the amino‐acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock‐freezing or by very slow cooling from room temperature to −75° before lithiation, give rise to different stereoselectivities (<i>Scheme 11</i>). The latter and the yields can also be influenced by tempering the lithiated species before (<i>Scheme 9</i>) or after addition of the electrophiles (<i>Scheme 12</i>). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80–95%). The results described are yet another demonstration that peptides may be backbone‐modified through Li enolates, and that whole series of analogous peptide derivatives with various side chains may thus be produced from a given precursor.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Part of the Ph.D. thesis of <i>H. G. B.</i>, Dissertation No. 10254, ETH‐Zürich, 1993</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Peptide Enolates. C‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides via dilithium azadienediolates</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Peptide Enolates. C‐Alkylation of Glycine Residues in linear tri‐, tetra‐, and pentapeptides via dilithium azadienediolates</title></titleInfo><name type="personal"><namePart type="given">Hans G.</namePart><namePart type="family">Bossler</namePart><affiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</affiliation><description>Part of the Ph.D. thesis of H. G. B., Dissertation No. 10254, ETH‐Zürich, 1993</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dieter</namePart><namePart type="family">Seebach</namePart><affiliation>Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</affiliation><affiliation>Correspondence address: Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH‐Zentrum, Universitätstrasse 16, CH–8092 Zürich</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>WILEY‐VCH Verlag GmbH</publisher><place><placeTerm type="text">Weinheim</placeTerm></place><dateIssued encoding="w3cdtf">1994-06-29</dateIssued><copyrightDate encoding="w3cdtf">1994</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">0</extent><extent unit="tables">0</extent><extent unit="references">57</extent></physicalDescription><abstract>The Boc‐protected tripeptides Boc‐Val‐Gly‐Leu‐OH (1), Boc‐Leu‐Sar‐Leu‐OH (2), Boc‐Leu‐Gly‐MeLeu‐OH (3), and Boc‐Val‐BzlGly‐Leu‐OMe (64), tetrapeptide Boc‐Leu‐Gly‐Pro‐Leu‐OH (9), and pentapeptides Boc‐Val‐Leu‐Gly‐Abu‐Ile‐OH (4), Boc‐Val‐Leu‐Sar‐MeAbu‐Ile‐OH (5), Boc‐Val‐Leu‐Gly‐MeAbu‐Ile‐OH (6), Boc‐Val‐Leu‐BzlGly‐BzlAbu‐Ile‐OH (7), and Boc‐Val‐Leu‐Gly‐BzlAbu‐Ile‐OH (8) are prepared by conventional methods (Schemes 4–7) or by direct benzylation of the corresponding precursors (Scheme 8). Polylithiations in THF give up to Li6 derivatives containing glycine, sarcosine or N‐benzylglycine Li enolate moieties (A–H). The polylithiated systems with a dilithium azadienediolate unit (C, F–H) are best generated by treatment with t‐BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (R)‐configuration (i.e. a D‐amino‐acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i‐PrI, allyl and benzyl bromide, ethyl bromoacetate, CO2, and Me2S2 (Schemes 11–13). No epimerizations of the starting materials (racemization of the amino‐acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock‐freezing or by very slow cooling from room temperature to −75° before lithiation, give rise to different stereoselectivities (Scheme 11). The latter and the yields can also be influenced by tempering the lithiated species before (Scheme 9) or after addition of the electrophiles (Scheme 12). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80–95%). The results described are yet another demonstration that peptides may be backbone‐modified through Li enolates, and that whole series of analogous peptide derivatives with various side chains may thus be produced from a given precursor.</abstract><relatedItem type="host"><titleInfo><title>Helvetica Chimica Acta</title></titleInfo><titleInfo type="abbreviated"><title>HCA</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><subject><genre>article-category</genre><topic>Article</topic></subject><identifier type="ISSN">0018-019X</identifier><identifier type="eISSN">1522-2675</identifier><identifier type="DOI">10.1002/(ISSN)1522-2675</identifier><identifier type="PublisherID">HLCA</identifier><part><date>1994</date><detail type="volume"><caption>vol.</caption><number>77</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>1124</start><end>1165</end><total>42</total></extent></part></relatedItem><identifier type="istex">AEE629B8C71271B54327612E7962EFC1D9170AE9</identifier><identifier type="ark">ark:/67375/WNG-RX12B67H-K</identifier><identifier type="DOI">10.1002/hlca.19940770424</identifier><identifier type="ArticleID">HLCA19940770424</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 1994 Verlag GmbH & Co. KGaA, Weinheim</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-L0C46X92-X">wiley</recordContentSource><recordOrigin>WILEY‐VCH Verlag GmbH</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/AEE629B8C71271B54327612E7962EFC1D9170AE9/metadata/json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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