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Design and Synthesis of Building Blocks for PPII‐Helix Secondary‐Structure Mimetics: A Stereoselective Entry to 4‐Substituted 5‐Vinylprolines
Author(s) -
Chiha Slim,
Soicke Arne,
Barone Matthias,
Müller Matthias,
Bruns Judith,
Opitz Robert,
Neudörfl JörgMartin,
Kühne Ronald,
Schmalz HansGünther
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201701584
Subject(s) - polyproline helix , chemistry , iminium , stereoselectivity , alkyl , alkylation , proline , stereochemistry , vinyl bromide , helix (gastropod) , bromide , side chain , amino acid , combinatorial chemistry , organic chemistry , catalysis , biochemistry , snail , peptide , ecology , polymer , biology
In the course of our studies towards the synthesis of proline‐based secondary‐structure mimetics, we developed a straightforward methodology for the diastereoselective preparation of 4‐alkyl‐5‐vinyl‐substituted proline derivatives. Starting from N ‐Boc‐protected tert ‐butyl pyroglutamate, α‐alkylation, lactam reduction and acid‐catalyzed methanolysis afforded 4‐alkyl‐5‐methoxyproline derivatives. After BF 3 ‐induced formation of an N ‐acyl‐iminium intermediate, the introduction of the 5‐vinyl side chain was achieved with high diastereoselectivity by using vinylmagnesium bromide in the presence of AlCl 3 or CuBr · SMe 2 to afford either the cis ‐ or the trans ‐product, respectively. The utility of the method was demonstrated in the rapid and efficient construction of new diproline mimetics rigidified in a polyproline‐type II helix (PPII) conformation.