Stereoselective Organocatalyzed Synthesis of α‐Fluorinated β‐Amino Thioesters and Their Application in Peptide Synthesis

Abstract

α-Fluorinated β-amino thioesters were obtained in high yields and stereoselectivities by organocatalyzed addition reactions of α-fluorinated monothiomalonates (F-MTMs) to N-Cbz- and N-Boc-protected imines. The transformation requires catalyst loadings of only 1 mol % and proceeds under mild reaction conditions. The obtained addition products were readily used for coupling-reagent-free peptide synthesis in solution and on solid phase. The α-fluoro-β-(carb)amido moiety showed distinct conformational preferences, as determined by crystal structure and NMR spectroscopic analysis.

Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobial α-polylysine

“…Thus, the antimicrobial effect was mainly caused by the cationic α-polylysine arms, which might destabilize the bacterial membrane and induce cytoplasmic leakage. Among all of the glycopolymer-polypeptide conjugates, the lowest MIC value was observed for the P(ManEMA) 10 -P(Lys) conjugate, and is twice that of the linear P(Lys). However, on the basis of molarity, all MIC values of the P(ManEMA) 10 -P(Lys) and P(ManEMA) 20 -P(Lys) conjugates were lower than that of the α-polylysine.…”

“…Among all of the glycopolymer-polypeptide conjugates, the lowest MIC value was observed for the P(ManEMA) 10 -P(Lys) conjugate, and is twice that of the linear P(Lys). However, on the basis of molarity, all MIC values of the P(ManEMA) 10 -P(Lys) and P(ManEMA) 20 -P(Lys) conjugates were lower than that of the α-polylysine. In addition, on the basis of the mass fraction of lysine units (Table 3), the P(ManEMA) 10 -P(Lys) conjugate exhibited MIC values lower than the linear P(Lys), namely at 7 µg mL −1 toward E. coli, 25 µg mL −1 toward P. aeruginosa, and 13 µg mL −1 toward both Staphylococci.…”

“…Sodium azide (99.5%), 2,2-bis(bromomethyl)propane-1,3-diol (98%), 2-bromopropionyl bromide (97%), triethylamine (99%), 10 and P(AcManEMA) 30 , respectively. P(AcManEMA) (3 g) was dissolved in 10 mL of methanol/ chloroform (1/1 volumetric ratio).…”

“…Inhibition of the interaction of the P(ManEMA)-P(Lys) with bacteria P(ManEMA) 10 -P(Lys) (115 mg, 0.01 mmol) and FITC (4 mg, 0.01 mmol) were dissolved in deionized water and stirred in the dark for 24 h. The mixture was dialyzed against deionized water for over 3 days and lyophilized to obtain FITC-labelled P(ManEMA) 10 -P(Lys) (yellow cotton-like solid, yield 90%). The FITC-labelled P(ManEMA) 10 -P(Lys) was dissolved in phosphate-buffered saline (PBS), or in PBS solution containing MeMan 0.1-0.3 M, to a concentration of 50 µg mL −1 .…”

“…Among the conventional well-established techniques to prepare synthetic peptides, solution-coupling and solidphase syntheses provide precise control over chain composition, with the drawback of employing multistep procedures in a tedious, time-consuming and expensive manner. [10][11][12] In technique allows the preparation of polypeptides with a narrowly defined chain length and intrachain composition. 14 Polypeptides consisting of a combination of lysine, alanine, phenylalanine, and leucine amino acids were prepared via the NCA-ROP technique, and the synthetic polypeptides showed microbiocidal activity against a wide range of pathogenic microorganisms, including clinically significant bacteria Serratia marcescens and fungi Candida albicans.…”