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3‐(Dimethylamino)‐2,2‐dimethyl‐2 H ‐azirin als α‐Aminoisobuttersäure(Aib)‐Äquivalent: Cyclische Depsipeptide durch direkte Amid‐Cyclisierung
Author(s) -
Obrecht Daniel,
Heimgartner Heinz
Publication year - 1987
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/hlca.19870700209
Subject(s) - chemistry , amide , azirine , depsipeptide , toluene , medicinal chemistry , hydrolysis , stereochemistry , ring (chemistry) , organic chemistry
3‐(Dimethylamino)‐2,2‐dimethyl‐2 H ,‐azirine as an α‐Aminoisobutyric‐Acid (Aib) Equivalent: Cyclic Depsipeptides via Direct Amid Cyclization In MeCN at room temperature, 3‐(dimethylamino)‐2,2‐dimethyl‐2 H ‐azirine ( 1 ) and α‐hydroxycarboxylic acids react to give diamides of type 8 ( Scheme 3 ). Selective cleavage of the terminal N , N ‐dimethylcarboxamide group in MeCN/H 2 O leads to the corresponding carboxylic acids 13 ( Scheme 4 ). In toluene/Ph SH , phenyl thioesters of type 11 are formed (see also Scheme 5 ). Starting with diamides 8 , the formation of morpholin‐2,5‐ diones 10 has been achieved either by direct amide cyclization via intermediate 1,3‐oxazol‐5(4 H )‐ones 9 or via base‐catalyzed cyclization of the phenyl thioesters 11 ( Scheme 3 ). Reaction of carboxylic acids with 1 , followed by selective amide hydrolysis, has been used for the construction of peptides from α‐hydroxy carboxylic acids and repetitive α‐aminoisobutyric‐acid (Aib) units ( Scheme 4 ). Cyclization of 14a, 17a , and 20a with HCI in toluene at 100° gave the 9‐, 12‐, and 15‐membered cyclic depsipeptides 15, 18 , and 21 , respectively.