Premium
Stereoselective Synthesis of [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐ N ‐(2‐hydroxyethoxy)‐ D ‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐ N ‐(2‐hydroxyethoxy)‐ L ‐valine]cyclosporin A
Author(s) -
Eberle Marcel K.,
Keese Reinhart
Publication year - 2010
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.201000175
Subject(s) - chemistry , tripeptide , epimer , stereochemistry , depsipeptide , stereoselectivity , trifluoromethyl , racemization , peptide , organic chemistry , biochemistry , alkyl , catalysis
Addition of various amines to the 3,3‐bis(trifluoromethyl)acrylamides 10a and 10b gave the tripeptides 11a – 11f , mostly as mixtures of epimers ( Scheme 3 ). The crystalline tripeptide 11f 2 was found to be the N‐terminal (2‐hydroxyethoxy)‐substituted ( R , S , S )‐ester HOCH 2 CH 2 O‐ D ‐Val(F 6 )‐MeLeu‐Ala‐O t Bu by X‐ray crystallography. The C‐terminal‐protected tripeptide 11f 2 was condensed with the N‐terminus octapeptide 2b to the depsipeptide 12a which was thermally rearranged to the undecapeptide 13a ( Scheme 4 ). The condensation of the epimeric tripeptide 11f 1 with the octapeptide 2b gave the undecapeptide 13b directly. The undecapeptides 13a and 13b were fully deprotected and cyclized to the [5‐[4,4,4,4′,4′,4′‐hexafluoro‐ N ‐(2‐hydroxyethoxy)‐ D ‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐hexafluoro‐ N ‐(2‐hydroxyethoxy)‐ L ‐valine]]cyclosporins 14a and 14b , respectively ( Scheme 5 ). Rate differences observed for the thermal rearrangements of 12a to 13a and of 12b to 13b are discussed.