Premium
Synthesis of 16‐Membered Cyclic Depsipeptides via Direct Amide Cyclization
Author(s) -
Koch Kristian N.,
Linden Anthony,
Heimgartner Heinz
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(20000119)83:1<233::aid-hlca233>3.0.co;2-1
Subject(s) - chemistry , depsipeptide , synthon , cyclic peptide , amide , azirine , monomer , oxazolone , stereochemistry , combinatorial chemistry , organic chemistry , ring (chemistry) , peptide , polymer , biochemistry
The 2,2‐disubstituted 2 H ‐azirin‐3‐amines 5 (3‐amino‐2 H ‐azirines) were used as synthons for α , α ‐disubstituted α ‐amino acids in the preparation of 16‐membered cyclic depsipeptides 13 . The linear precursors containing four α , α ‐disubstituted α ‐amino acids, the pentapeptides 12 , were synthesized from β ‐hydroxy acids 4 via the `azirine/oxazolone method' ( Scheme 2 ). The 16‐membered cyclic depsipeptides 13 were prepared via `direct amide cyclization' in good‐to‐excellent yields ( Schemes 3 and 4 ). In addition to the desired cyclic monomer 13 , which was obtained as the main product, the cyclodimer 14 could also be isolated. The cyclization conditions were investigated and found to be optimum with HCl in toluene at 100°. The structure and conformation of the cyclic depsipeptide 13b was established by X‐ray crystallography.