Preparation of the β3‐Homoselenocysteine Derivatives Fmoc‐β3hSec(PMB)‐OH and Boc‐β3hSec(PMB)‐OH for Solution and Solid‐Phase‐Peptide Synthesis and Selenoligation |
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| Authors: | Oliver Flögel Giulio Casi Donald Hilvert Dieter Seebach |
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| Affiliation: | 1. Laboratorium für Organische Chemie, Department Chemie und Angewandte Biowissenschaften, Eidgen?ssische Technische Hochschule, ETH‐Zürich, H?nggerberg, HCI, Wolfgang‐Pauli‐Strasse 10, CH‐8093 Zürich, (phone: +41?44?632?29?90;2. fax: +41?44?632?11?44);3. Postdoctoral Fellowship at ETH‐Zürich 2004/2006, financed by Deutsche Forschungsgemeinschaft, Schweizer Nationalfonds (Project No. 200020‐109065), and Novartis Pharma AG, Basel.;4. Part of the projected Ph.D. thesis of G.C., ETH‐Zürich. |
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| Abstract: | The title compounds, 4 and 7 , have been prepared from the corresponding α‐amino acid derivative selenocystine ( 1 ) by the following sequence of steps: cleavage of the Se? Se bond with NaBH4, p‐methoxybenzyl (PMB) protection of the SeH group, Fmoc or Boc protection at the N‐atom and Arndt–Eistert homologation (Schemes 1 and 2). A β3‐heptapeptide 8 with an N‐terminal β3‐hSec(PMB) residue was synthesized on Rink amide AM resin and deprotected (‘in air’) to give the corresponding diselenide 9 , which, in turn, was coupled with a β3‐tetrapeptide thiol ester 10 by a seleno‐ligation. The product β3‐undecapeptide was identified as its diselenide and its mixed selenosulfide with thiophenol (Scheme 3). The differences between α‐ and β‐Sec derivatives are discussed. |
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| Keywords: | Selenocysteine Amino acids Homoselenocysteine Selenoligation Peptides Arndt– Eistert homologation Solid‐phase peptide synthesis (SPPS) |
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