Diboronic Acid Anhydride-Catalyzed Direct Peptide Bond Formation Enabled by Hydroxy-Directed Dehydrative Condensation

Abstract

We report the catalytic direct peptide bond formations via dehydrative condensation of β-hydroxy-α-amino acids, affording the serine, threonine, or β-hydroxyvaline-derived peptides in high to excellent yields with high functional group tolerance, minimum epimerization, and excellent chemoselectivity. The key to the success of these atom-economical transformations is the use of diboronic acid anhydride catalyst for the hydroxy-directed reactions.

On the Copper-Promoted Backbone Arylation of Histidine-Containing Peptides Using Triarylbismuthines

“…N α -((tert-butoxycarbonyl)-L-seryl)-N τ -trityl-L-histidinate (1h) This compound has been previously reported (21) : Procedure A was followed starting from L-Boc-Ser-OH (92 mg, 446 µmol) and HCTU. The resulting crude product was purified on silica gel (20 to 80% EtOAc/Hex) to afford 1h as a white solid (76 mg, 28%): Mp 86 -88 °C; Rf = 0.21 (70% EtOAc/Hex); IR (ATR)/𝝂 ": 3300, 2933, 1713, 1667, 1492, 1445, 1390, 1365, 1240, 1159, 1133, 1086, 1056, 1034, 1002, 840, 748, 701, 660, 638 cm -1 .…”

“…This compound has been reported previously. 21 Procedure A was followed starting from l -Boc-Ser-OH (92 mg, 446 μmol) and HCTU. The resulting crude product was purified by column chromatography (silica gel, 20–80% EtOAc/hexane) to afford 1h as a white solid.…”

Heteroelement Analogues of Benzoxaborole and Related Ring Expanded Systems

“…However, unlike benzoxadiboroles, the B-O-B linkage in 32 seems to be rather stable as there are no data which might indicate that a reversible hydrolysis to naphthalene-1,8-diboronic acid occurs to any appreciable extent. Compound 32 was used as a starting material for synthesis of a few 1H,3H-naphth[l,8-cd][l,2,6]oxadiborin derivatives (34)(35)(36)(37) where hydroxyl groups were replaced with OMe, Cl, Me [23], or mesityl (Mes) substituents [24], respectively. Very recently, a structurally extended analogue of 32 based on bicyclohexene-perinaphthalene framework 38 was obtained using an analogous protocol involving brominelithium exchange in an appropriate dibromide, followed by boronation.…”

“…Remarkably, 41-42 were reported as efficient catalysts of dehydrative amidation of carboxylic acids with amine substrates. Initially, they were employed for efficient preparation of various α-and β-hydroxy substituted amides [32] but thereafter also proved effective in catalyzing the formation of Weinreb amides [33,34] as well as various oligopeptides [35]. In the former case, the proposed mechanism of the catalytic process involves the cooperation of the two boron atoms in 41-42, which enables the formation of a cyclic mixed anhydride with carboxylic acid molecule, as evidenced by the ESI MS spectrum; this is followed by an attack of amine on the activated carbonyl group (Scheme 15) [32].…”

Synthesis of Dipeptides and Ruthenium-Phenanthroline Derivative for Photo Redox Studies

“…(scheme-1) Alternatively, dipeptide acid 2a was prepared from phthalimido ethanol 18 8, which on oxidation to acid product 19 9 followed by acid chloride 20 conversion gives 10 in 91% yield, which was esterified to MPM ester 21 11 by using MPM-OH, the phthalide group is cleaved by 40% monomethyl amine to get glycine MPM ester 22 12 in 55% yield. (scheme-2) Similarly, corresponding symmetrical dipeptides from isoleucine 23,24 , leucine [25][26][27] and phenylalanine [28][29][30] were synthesized in four steps each to get 2b, 2c, and 2d respectively.…”