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  • Unnatural Lysines with Reduced Sidechain N ‐Basicity: Synthesis of N ‐trifluoroethyl Substituted Lysine and Homologs
Title: Unnatural Lysines with Reduced Sidechain N ‐Basicity: Synthesis of N ‐trifluoroethyl Substituted Lysine and Homologs
Abstract The syntheses are reported of Nϵ‐(2,2,2‐trifluoroethyl)‐D,L‐lysine (tFK) and Nζ‐(2,2,2‐trifluoroethyl)‐D,L‐homolysine (tFK+1) from amino alcohols HO−(CH2)n−NH2. The syntheses involve reductive amination, Appel bromination, and the stereoselective bond formation between Cα of the amino acid and the fluorinated alkyl chain in the Schöllkopf bislactim amino acid synthesis. The methyl esters of the fluorinated amino acids are the relevant substrates for oligopeptide synthesis. With theR‐Schöllkopf reagent, we stereoselectively generated methyl Nϵ‐boc‐Nϵ‐(2,2,2‐trifluoroethyl)‐L‐lysinate and methyl Nζ‐boc‐Nζ‐(2,2,2‐trifluoroethyl)‐L‐homolysinate. Products and intermediates were characterized by 1H NMR, 13C NMR, COSY, HSQC, and LCMS. A variety of N‐functionality may be introduced by reacting hemiacetals with different appendages. This fluorine modification reduces the sidechain N‐basicity by combined ‐I effect of the three fluorines. This effect increases the [amine]/[ammonium ion] ratio of the sidechain amine in lysine to facilitate carbamylation at lower pH conditions.  more » « less
Award ID(s):
2153206
PAR ID:
10511003
Author(s) / Creator(s):
;
Publisher / Repository:
Chemistry Europe
Date Published:
Journal Name:
ChemistrySelect
Volume:
7
Issue:
48
ISSN:
2365-6549
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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