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- Title
Preparation of Protected 2- and 3-Homocysteine, 2- and 3-Homohistidine, and 2-Homoserine for Solid-Phase SynthesesPartially published in preliminary communications [1]?[2].
- Authors
Grald Lelais; Peter Micuch; Delphine Josien-Lefebvre; Francesco Rossi; Dieter Seebach
- Abstract
The Ser, Cys, and His side chains play decisive roles in the syntheses, structures, and functions of proteins and enzymes. For our structural and biomedical investigations of -peptides consisting of amino acids with proteinogenic side chains, we needed to have reliable preparative access to the title compounds. The two 3-homoamino acid derivatives were obtained by ArndtEistert methodology from Boc-His(Ts)-OH and Fmoc-Cys(PMB)-OH (Schemes 4;24), with the side-chain functional groups' reactivities requiring special precautions. The 2-homoamino acids were prepared with the help of the chiral oxazolidinone auxiliary DIOZ by diastereoselective aldol additions of suitable Ti-enolates to formaldehyde (generated in situ from trioxane) and subsequent functional-group manipulations. These include OH?OtBu etherification (for 2hSer; Schemes 4;5 and 6), OH?STrt replacement (for 2hCys; Scheme 4;7), and CH2OH?CH2N3?CH2NH2 transformations (for 2hHis; Schemes 4;911). Including protection/deprotection/re-protection reactions, it takes up to ten steps to obtain the enantiomerically pure target compounds from commercial precursors. Unsuccessful approaches, pitfalls, and optimization procedures are also discussed. The final products and the intermediate compounds are fully characterized by retention times (tR), melting points, optical rotations, HPLC on chiral columns, IR, 1H- and 13C-NMR spectroscopy, mass spectrometry, elemental analyses, and (in some cases) by X-ray crystal-structure analysis.
- Subjects
SPECTRUM analysis; AMINO acids; ORGANIC acids; ORGANIC compounds
- Publication
Helvetica Chimica Acta, 2004, Vol 87, Issue 12, p3131
- ISSN
0018-019X
- Publication type
Article