194724-09-9

Upstream product

• 16881-34-8 N-benzyloxycarbonyl-L-phenylalanine t-butyl ester 
• 1161-13-3 N-Cbz-L-Phe 
• 63-91-2 L-phenylalanine 
• 3182-95-4 L-Phenylalaninol 
• 115-11-7 isobutene 

Relevant academic research and scientific papers

Backbone amide linker (BAL) strategy for solid-phase synthesis of C-terminal-modified and cyclic peptides

Peptide targets for synthesis are often desired with C-terminal end groups other than the more usual acid and amide functionalities. Relatively few routes exist for synthesis of C-terminal-modified peptides-including cyclic peptides - by either solution or solid-phase methods, and known routes are often limited in terms of ease and generality. We describe here a novel Backbone Amide Linker (BAL) approach, whereby the growing peptide is anchored through a backbone nitrogen; thus allowing considerable flexibility in management of the termini. Initial efforts on BAL have adapted the chemistry of the tris(alkoxy)benzylamide system exploited previously with PAL anchors. Aldehyde precursors to PAL, e.g. 5-(4-formyl-3,5-dimethoxyphenoxy)valeric acid, were reductively coupled to the α-amine of the prospective C-terminal amino acid, which was blocked as a tert-butyl, allyl, or methyl ester, or to the appropriately protected C-terminal-modified amino acid derivative. These reductive aminations were carried out either in solution or on the solid phase, and occurred without racemization. The secondary amine intermediates resulting from solution amination were converted to the 9-fluorenylmethoxycarbonyl (Fmoc)-protected preformed handle derivatives, which were then attached to poly(ethylene glycol)-polystyrene (PEG-PS) graft or copoly(styrene - 1% divinylbenzene) (PS) supports and used to assemble peptides by standard Fmoc solid-phase chemistry. Alternatively, BAL anchors formed by onresin reductive amination were applied directly. Conditions were optimized to achieve near-quantitative acylation at the difficult step to introduce the penultimate residue, and a side reaction involving diketopiperazine formation under some circumstances was prevented by a modified protocol for Nα-protection of the second residue/ introduction of the third residue. Examples are provided for the syntheses in high yields and purities of representative peptide acids, alcohols, N,N-dialkylamides, aldehydes, esters, and head-to-tail cyclic peptides. These methodologies avoid postsynthetic solution-phase transformations and are ripe for further extension.

Palladium-catalyzed coupling of optically active amines with aryl bromides

The coupling of enantiomerically enriched amines with aryl bromides produces the corresponding N-aryl derivatives. The choice of ligand in the palladium-catalyzed coupling is critical to the formation of the anilines without loss of enantiomeric purity. W