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L ‐Phenylalanine Cyclohexylamide: A simple and convenient auxiliary for the synthesis of optically pure α,α‐disubstituted ( R )‐ and ( S )‐amino acids
Author(s) -
Obrecht Daniel,
Bohdal Udo,
Broger Clemens,
Bur Daniel,
Lehmann Christian,
Ruffieux Ruth,
Schönholzer Peter,
Spiegler Clive,
Müller Klaus
Publication year - 1995
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.19950780305
Subject(s) - chemistry , phenylalanine , amino acid , optically active , peptide synthesis , stereochemistry , crystal structure , absolute configuration , series (stratigraphy) , crystal (programming language) , crystallography , organic chemistry , biochemistry , paleontology , computer science , programming language , biology
This work describes L ‐phenylalanine cyclohexylamide ( 5c ) as a simple, cheap, and powerful chiral auxiliary for the synthesis of a series of optically pure α,α‐disubstituted ( R )‐ and ( S )‐amino acids of type 1 , such as ( R )‐ and ( S )‐2‐methyl‐phenylalanine ( 1a ), ( R )‐ and ( S )‐2‐methyl‐2‐phenylglycine ( 1b ), and ( R )‐ and ( S )‐2‐methylvaline ( 1c ; Scheme 3 ). These amino acids were efficiently transformed into the suitably protected and activated amino acid building blocks ( R )‐ and ( S )‐ 12b and ( R )‐ and ( S )‐ 12c ( Scheme 4 ) which are ready for incorporation into peptides by solution or solid‐phase techniques. Based on the crystal structures of 6b, 6c , and 7a belonging to the diastereoisomeric peptides series 6 and 7 , the absolute configurations of each member of the series were determined. β‐Turn geometries of type II′ and I were observed for 6b and 7a , respectively, whereas 6c crystallized in an extended conformation. The impacts of side‐chain variation on conformation and crystal packing of these triamides are discussed.