Solid-Phase Synthesis with Tris(alkoxy)benzyl Backbone Amide Linkage (BAL)[≠]

Methods for the Peptide Synthesis and Analysis

“…Numerous amino acids have been used for side-chain anchoring, including Asx/Glx [220][221][222][223][224][225][226], Lys/Orn [220,227], Ser/Thr [220,228], Tyr [220,224,229], His [230,231], and Cys [232,233], on the usual supports and linkers for peptide synthesis. BAL anchoring: The original concept of the BAL linker [234,235] involves the attachment of a backbone amide nitrogen to an appropriate handle. Since linkage does not rely on the C-terminal carboxyl, the BAL linker allows the preparation of a large variety of C-terminal modified peptides [236], including cyclic peptides.…”

Electrophile Cleavable Linker Units

“…[184,185] Although C-terminal modified peptides, heterocycles and other small organic molecules have been synthesized through peptide bond anchoring using the PAL, syntheses of primary or secondary amine derivatives using the BAL was popularized by Albericio and Barany. [184] The BAL functional moiety can be introduced to a wide variety of aminomethylated resins by ligation reactions with 5-(4-formyl-3,5-dimethoxyphenoxy)pentanoic acid (i.e.…”

“…The recovered resin 198 could reuse to operate the same reaction after the propionation reaction (Scheme 2.29).Asymmetric syntheses of the α-chiral carboxylic acids and their esters using the polymer-bound oxazoline were reported by McManus and coworkers [251]. Trans-(4S, 5S)-2-ethyl-4-(hydroxymethyl)-5-phenyl-2-oxazoline(199) was attached to the Merrifield resin 2a to give the polymer-bound oxazoline 200. Benzylation of the optically active oxazoline 195 followed by an acid catalyzed solvolysis of the resulting product 201 provided (S)-ethyl 2-methyl-3-phenylpropoanoate (202) in 43-48% with 56% ee.…”

Carbohydrates as templates for control of distance-geometry in de novo-designed proteins

“…Briefly, the syntheses followed a standard BAL strategy [58,59,62], commencing with coupling of a PALdehyde handle to aminofunctionalized resin, followed by anchoring of the glycinal terminal by reductive amination with aminoacetaldehyde dimethyl acetal. Next, acylation of the secondary nitrogen was achieved with (Fmoc-Gly) 2 O, whereas subsequent chain elongation followed standard Fmoc methodology for solid-phase peptide synthesis (SPPS).…”