Abstract
A rapid and efficient strategy has been developed for the general synthesis of complex peptide aldehydes. Nα-Benzyloxycarbonylamino acids were converted to protected aldehyde building blocks for solid-phase synthesis in four steps and moderate overall yields. The aldehydes were protected as 1,3-dioxolanes except for one case where a dimethyl acetal was used. These protected amino aldehyde monomers were then incorporated onto 5-[(2 or 4)-formyl-3,5-dimethoxyphenoxy]butyryl-resin (BAL-PEG-PS) by reductive amination, following which the penultimate residue was introduced by HATU-mediated acylation. The resultant resin-bound dipeptide unit, anchored by a backbone amide linkage (BAL), was extended further by routine Fmoc chemistry procedures. Several model peptide aldehydes were prepared in good yields and purities. Some epimerization of the C-terminal residue occurred (10% to 25%), due to the intrinsic stereolability conferred by the aldehyde functional group, rather than any drawbacks to the synthesis procedure. Coyright
Original language | English (US) |
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Pages (from-to) | 525-535 |
Number of pages | 11 |
Journal | Journal of Peptide Science |
Volume | 11 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2005 |
Keywords
- 1,3-dioxolanes
- Backbone amide linker (BAL)
- Dimethyl acetals
- Peptide aldehydes
- Protease inhibitors
- Solid-phase synthesis