Benzotriazol-1-yl-sulfonyl azide, a new crystalline, stable, and easily available diazotransfer reagent provides N-(α-azidoacyl)benzotriazoles convenient for N-, O-, C- and S-acylations. The efficient syntheses of various amides, azido protected peptides, esters, ketones and thioesters is reported together with a wide range of azides (including α-azido acids from α- amino acids in partially aqueous conditions) and diazo compounds.

Stable and easily accessible N-acylbenzotriazoles, derived from a variety of aliphatic, unsaturated, (hetero)aromatic, and N-protected alpha-amino carboxylic acids, were reacted with Grignard and heteroaryllithium reagents to afford corresponding ketones in good to excellent yields.

Chemical ligation via O- to N-acyl transfer of O-acylated serine containing peptides affords serine containing native peptides via 8- and 11-membered cyclic transition states opening the door to a wide variety of potential applications to peptide elaboration. The feasibility of these traceless chemical ligations is feasible as supported by computation.

Optically pure conjugates of quinolone antibiotics with naturally occurring amino acids are synthesized in 40-98% yields.

O-Acylation of N-Boc-protected-serine and -threonine with N-Pg-(a-aminoacyl)benzotriazoles afforded the chiral O-acylated isodipeptides at 23 C in yields of 74-91%.The synthesis of peptides and proteins is of great importance to the understanding of biological functions. The solid-phase synthesis of peptides with ''difficult sequences'' remains problematic due to low yields and purity. 1 In addition, intermolecular hydrophobic interactions in ''difficult sequences'' can promote aggregation in solution and hydrogen bond networks in resinbound peptides can form extended structures such as b-sheets. 1b-c,2 Kiso et al. 1d demonstrated that the introduction of an O-acyl in place of an N-acyl residue within a peptide backbone significantly altered the secondary structure of native peptides. Furthermore, these ''O-acyl isopeptides'' or ''click peptides'' ‡ are more hydrophilic, and easier to purify by HPLC. 1d He found that a subsequent O-N intramolecular acyl migration, triggered by change in pH, could rapidly generate a target natural peptide under physiological conditions (pH 7.4) (Fig. 1). 1c,3a This ''O-acyl isopeptide method'' 3 has been used to develop new water-soluble taxoid prodrugs, 4 HIV-1 protease inhibitors, 5 the anti-tumor agent, paclitaxel, 6 difficult sequence-containing peptides including Ac-Val-Val-Ser-Val-Val-NH 2 , 1b,4,7 Alzeheimer's disease-related amyloid b peptide (Ab) 1-42, 4,7-13 and cyclic peptides. 14