Synthesis of δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine and some carbon-13 and nitrogen-15 labelled isotopomers

Abstract

valine (7c), and 6-(L-a-aminoadipoyl)-L-[3-13C]cysteinyl-D-[3-13C, 15N]valine (7d) were prepared by conventional means using benzyl-based protective groups.(7a),4s part of a research programme designed to study the cell-free conversion of the tripeptide 6-( 1,-aminoadipoy1)c-cysteinyl-D-valine into isopenicillin N by means of 13C n .in.r. spectroscopy we required several labelled isotiipomers of the tripeptide. Three syntheses of this peptide have been reported I-3 all of which differ in the type of protective groups used and, consequently, in the number and nature of the subsequent deprotection steps

Unexpected Oxidation of a Depsipeptide Substrate Analogue in Crystalline Isopenicillin N Synthase

“…[41] This protected amino acid was then coupled to doubly protected L-aaminoadipic acid using iso-butylchloroformate methodology. [42] Then caesium carbonate-mediated coupling of the dipeptide and (2S)-a-bromoisovaleric acid tert-butyl ester was accomplished following the procedure of Lerchen and Kunz, [43] prior to trifluoroacetic acid deprotection [44] to give the substrate analogue AmCOV 15. Crystallisation and turnover experiments: Crystals of IPNS: Fe II :AmCOV were grown anaerobically following the protocol described previously.…”

Interactions of Isopenicillin N Synthase with Cyclopropyl-Containing Substrate Analogues Reveal New Mechanistic Insight,

“…cysteine (24), using EEDQ methodology. This gave the fully protected tripeptide as a mixture of two diastereomers, from which the desired L,L,D-product 10 was isolated by chromatography as the less polar diastereomer (23) (stereochemistry further confirmed by crystallographic data).…”

N‐terminal amino acid sequence and some properties of isopenicillin‐N synthetase from Cephalosporium acremonium

“…was prepared according to Baldwin et al [4]. C. acremonium CO728 was a gift from Glaxo, Ulverston, England.…”