Facile and Mild Synthesis of Linear and Cyclic Peptides via Thioesters

Abstract

Thioester-mediated peptide bond formation has recently garnered a lot of attention, most notably in its relevance to condensation of large peptide fragments. Herein, a simple and general ligation method for the preparation of linear and cyclic peptides, starting from peptide thioester, mainly p-chlorophenyl, precursors is reported. The inherent advantages of this method are the low epimerization, reduced dimerization, use of mild reaction conditions, and elimination of superfluous coupling reagents.

HF‐Free Boc Synthesis of Peptide Thioesters for Ligation and Cyclization

“…Recently, peptide thiophenyl esters were shown to cyclize 2c. Independently, the Houghten group cyclized peptide MPAL thioesters 2b.…”

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

“…Leu-enkephalin 1 ( Table 1 , entry 1) could be successfully synthesized following the route mentioned above ( Scheme 2 ). Besides, the precursor 2 of a cyclic heptapeptide pseudostellarin D [ 37 – 39 ] was also obtained via SPPS in good yield ( Table 1 , entry 2), the cyclization of 2 to give pseudostellarin D using FPID/(4-MeOC 6 H 4 ) 3 P will be described in the following part. Moreover, angiotensin I converting enzyme (ACE) inhibitory peptides, widely exist in plants and animals, can serve as potential antihypertensive pharmaceuticals [ 40 – 42 ].…”

“…The first one was reported by Belagali in 1999, pseudostellarin D was obtained by the cyclization of the linear heptapeptide peptide-PNP ester, which is known as the p -nitrophenyl ester method ( Scheme 4 , method A). The other one was described by Agrigento and co-workers, the cyclization was completed via the p -chlorophenyl thioester method with peptide-thioester being the precursor ( Scheme 4 , method B) [ 39 ]. Herein, we realized the synthesis of pseudostellarin D following the same cyclization strategy mentioned above by direct coupling of the precursor 2 without any protecting group utilizing the system of FPID/(4-MeOC 6 H 4 ) 3 P ( Scheme 4 , method C).…”

HF‐Free Boc Synthesis of Peptide Thioesters for Ligation and Cyclization

“…Peptide thioesters have been successfully cyclized in the absence of N‐terminal cysteine. Recently, peptide thiophenyl esters were shown to cyclize . Independently, the Houghten group cyclized peptide MPAL thioesters .…”