Safe and efficient Boc‐SPPS for the synthesis of glycopeptide‐α‐thioesters‡. (6th January 2014)

• Record Type: Journal Article
• Authors: Izumi, Masayuki; Murakami, Masumi; Okamoto, Ryo; Kajihara, Yasuhiro; Becker, Christian
• Is Part Of: Journal of peptide science. Volume 20:Number 2(2014:Feb.)
• Page Start: 98
• Page End: 101
• Publication Date: 2014-01-06
• Subjects: Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2608
• Languages: English
• ISSNs: 1075-2617

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Boc‐solid phase peptide synthesis is useful for the preparation of peptide‐<alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgg40bjz5vk" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" overflow="scroll" altimg="urn:x-wiley:10752617:media:psc2608:psc2608-math-0002" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi mathvariant="normal">α</mml:mi></mml:math></alternatives>‐thioesters. However, this strategy usually employs hydrogen fluoride for the final deprotection step. These strongly acidic conditions cannot be applied for the synthesis of acid‐labile glycopeptide‐<alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgg40bjz5t1" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" overflow="scroll" altimg="urn:x-wiley:10752617:media:psc2608:psc2608-math-0003" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi mathvariant="normal">α</mml:mi></mml:math></alternatives>‐thioesters. The protocol presented here is a modified <italic>in situ neutralization</italic> Boc‐solid phase peptide synthesis employing 10% sulfuric acid/dioxane conditions for intermediate Boc removal and TfOH for the final side‐chain deprotection step. These conditions were found to be applicable for the synthesis of acid‐labile glycopeptide‐<alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgg40bjz5sg" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" overflow="scroll" altimg="urn:x-wiley:10752617:media:psc2608:psc2608-math-0004" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi mathvariant="normal">α</mml:mi></mml:math></alternatives>‐thioesters. In this protocol, a glycopeptide is synthesized as <alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgg40bjz5rx" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" overflow="scroll" altimg="urn:x-wiley:10752617:media:psc2608:psc2608-math-0005" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>α</mml:mi><mml:mo>‐</mml:mo></mml:math></alternatives> thioester on a thiol linker, and the product glycopeptide‐<alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgg40bjz5qc" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" overflow="scroll" altimg="urn:x-wiley:10752617:media:psc2608:psc2608-math-0006" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi mathvariant="normal">α</mml:mi></mml:math></alternatives>‐thioester is released from the resin by thiolysis after side‐chain deprotection step with an acid cocktail containing TfOH instead of hydrogen fluoride. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.</p> </abstract>