A solid-phase synthetic route to unnatural amino acids with diverse side-chain substitutions.
Reacting imine derivatives of resin-bound amino acids with alpha,omega-dihaloalkanes provides highly versatile intermediates to racemic alpha,alpha-disubstituted amino acids with a wide variety of side-chain functionality. Two strategies were developed to convert the intermediate omega-chloro or omega-bromo derivatives to the desired products. Together, they allow the creation of amino acids with diverse functionalities (omega-chlorides, nitriles, azides, acetates, thioacetates, thioethers, secondary and tertiary aliphatic amines, and anilines) placed at varying chain lengths (2-5) from the alpha-center of the amino acid.
Scott
William L
WL
Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, Indiana 46285, USA. wscott@chem.iupui.edu
O'Donnell
Martin J
MJ
Delgado
Francisca
F
Alsina
Jordi
J
D000478:Alkylation; D000596:Amino Acids / Q000737:chemistry; D000597:Amino Acids, Branched-Chain / Q000138:chemical synthesis* / Q000737:chemistry*; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D006846:Hydrocarbons, Halogenated / Q000737:chemistry; D006868:Hydrolysis; D007097:Imines / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D012116:Resins, Plant / Q000737:chemistry; D013696:Temperature
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D001386:Azides; D006846:Hydrocarbons, Halogenated; D007097:Imines; D007783:Lactones; D009570:Nitriles; D012116:Resins, Plant; D011392:Proline