𝔖 Bobbio Scriptorium
✦   LIBER   ✦

The ‘Azirine/Oxazolone Approach’ to the Synthesis of Aib-Pro Endothiopeptides

✍ Scribed by Artur Budzowski; Anthony Linden; Heinz Heimgartner

Publisher
John Wiley and Sons
Year
2008
Tongue
German
Weight
323 KB
Volume
91
Category
Article
ISSN
0018-019X

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

The reaction of methyl N‐(2,2‐dimethyl‐2__H__‐azirin‐3‐yl)‐L‐prolinate (2a) with thiobenzoic acid at room temperature gave the endothiopeptide Bz‐Aib__Ψ__[CS]‐Pro‐OMe (7) in high yield. In an analogous manner, (benzyloxy)carbonyl (Z)‐protected proline was transformed into the thioacid, which was reacted with 2a to give the endothiotripeptide Z‐Pro‐Aib__Ψ__[CS]‐Pro‐OMe (12). The corresponding thioacid of 7 was prepared in situ via saponification, formation of a mixed anhydride, and treatment with H~2~S. A second reaction with 2a led to the endodithiotetrapeptide 9, but extensive epimerization at Pro^2^ was observed. Similarly, saponification of 12 and coupling with either 2a or H‐Phe‐OMe and 2‐(1__H__‐benzotriazol‐1‐yl)‐1,1,3,3‐tetramethyluronium tetrafluoroborate/1‐hydroxy‐1__H__‐benzotriazole (TBTU/HOBt) gave the corresponding endothiopeptides as mixtures of two epimers. The synthesis of the pure diastereoisomer Bz__Ψ__[CS]‐Aib‐Pro‐Aib__Ψ__[CS]‐N(Me)Ph (21) was achieved via isomerization of 7 to Bz__Ψ__[CS]‐Aib‐Pro‐OMe (16), transformation into the corresponding thioacid, and reaction with N,2,2‐trimethyl‐N‐phenyl‐2__H__‐azirin‐3‐amine (1a). The structures of 12 and 21 were established by X‐ray crystallography.

📜 SIMILAR VOLUMES

Synthesis of the endothiopeptide BOC-Trp
Synthesis of the endothiopeptide BOC-Trp-Ile-Ala-Aib-Ile-ValΨ[CSNH]Aib-Leu-Aib-Pro-OMe by a variation of the ‘azirine/oxazolone method’
✍ Jürg Lehmann; Anthony Linden; Heinz Heimgartner 📂 Article 📅 1998 🏛 Elsevier Science 🌐 French ⚖ 900 KB

The synthesis of the decaendothiopepfide BOC-Trp-Ile-Ala-Aib-lle-Val~F[CSNH]Aib-Leu -Aib-Pro-OMe is described. The introduction of the thioamide group next to the bulky Aib occurred via a variation of the 'azirine/oxazolone method' without epimerisation. The structure of the decaendothiopeptide was

Synthesis of Poly-Aib Oligopeptides and
Synthesis of Poly-Aib Oligopeptides and Aib-Containing Peptides via the ‘Azirine/Oxazolone Method’, and Their Crystal Structures
✍ Ingeborg Dannecker-Dörig; Anthony Linden; Heinz Heimgartner 📂 Article 📅 2011 🏛 John Wiley and Sons 🌐 German ⚖ 348 KB

The protected poly-Aib oligopeptides Z-(Aib) n -N(Me)Ph with n ¼ 2 -6 were prepared according to the azirine/oxazolone method, i.e., by coupling amino or peptide acids with 2,2,N-trimethyl-N-phenyl-2H-azirin-3-amine (1a) as an Aib synthon (Scheme 2). Following the same concept, the segments Z-(Aib)

Synthesis of the protected 6–16 segment
Synthesis of the protected 6–16 segment of zervamicin II-2, an application of the azirine/oxazolone method
✍ Nicolas Pradeille; Heinz Heimgartner 📂 Article 📅 2003 🏛 John Wiley and Sons 🌐 English ⚖ 158 KB

## Abstract The protected 11 amino acid segment (6–16) of the peptaibol zervamicin II‐2 was synthesized by using the ‘azirine/oxazolone method’ for the introduction of all Aib residues. Whereas a 2,2‐dimethyl‐2__H__‐azirin‐3‐amine was used as the building block for Aib(7), methyl 2,2‐dimethyl‐2__H_