Solid-phase synthesis of multiple classes of peptidomimetics from versatile resin-bound aldehyde intermediates.
A wide variety of highly substituted lactam containing peptidomimetic scaffolds are prepared by solid-phase synthesis from a single, versatile class of resin-bound aldehyde intermediates (1). These include monocyclics 3, bicyclics 4, tricyclics 5, and tetracyclics 6. The key intermediate 1 is readily synthesized from resin-bound natural or unnatural alpha-amino acids. The synthetic procedures permit the construction of a large diversity of substitution patterns for ready use in combinatorial chemistry. In every case, the release of final products from resin is by a cyclitive cleavage process. Since this depends on successful completion of multiple intermediate synthetic steps, the products are often quite pure, even though previous steps involve only a filtration workup. The mild conditions for many of these synthetic procedures offer the promise of using this chemistry in peptide fragment condensations to produce modified peptides, at either the N-terminus or C-terminus, or as individually assembled peptide segments with a wide variety of conformationally restricted peptidomimetic linkers at the point of juncture.
Scott
William L
WL
Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana 46202-3274, USA. wscott@chem.iupui.edu
Martynow
Jacek G
JG
Huffman
John C
JC
O'Donnell
Martin J
MJ
D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry*; D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D012117:Resins, Synthetic / Q000138:chemical synthesis / Q000737:chemistry
D000447:Aldehydes; D000577:Amides; D000588:Amines; D001643:Bridged Bicyclo Compounds; D007769:Lactams; D007783:Lactones; D010455:Peptides; D011137:Polystyrenes; D012117:Resins, Synthetic