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A Novel 2 H ‐Azirin‐3‐amine as a Dipeptide (Aib‐Hyp) Synthon
Author(s) -
Breitenmoser Roland A.,
Hirt Thomas R.,
Luykx Roeland T. N.,
Heimgartner Heinz
Publication year - 2001
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 - 10.1002/1522-2675(20010418)84:4<972::aid-hlca972>3.0.co;2-m
Subject(s) - chemistry , dipeptide , synthon , amine gas treating , reagent , stereochemistry , amino acid , peptide , medicinal chemistry , organic chemistry , biochemistry
The synthesis of methyl (2 S ,4 R )‐4‐(benzyloxy)‐ N ‐(2,2‐dimethyl‐2 H ‐azirin‐3‐yl)prolinate ( 10 ), a novel 2 H ‐azirin‐3‐amine (`3‐amino‐2 H ‐azirine'), is described ( Scheme 1 ). The reaction of methyl (2 S ,4 R )‐ N ‐(2‐methylpropanoyl)‐4‐(benzyloxy)prolinate ( 7 ) with Lawesson reagent gave methyl (2 S ,4 R )‐4‐(benzyloxy)‐ N ‐[2‐(methylthio)propanoyl]prolinate ( 8 ) and consecutive treatment with COCl 2 , 1,4‐diazabicyclo[2.2.2]octane (DABCO), and NaN 3 led to 10 . The use of 10 as a building block of the dipeptide Aib‐Hyp (Aib=2‐aminoisobutyric acid, Hyp=(2 S ,4 R )‐4‐hydroxyproline) is demonstrated by the syntheses of several model peptides ( Scheme 2 and Table ). The benzyl protecting group of the 4‐OH function in Hyp in the model peptides has been removed in good yields.