Fmoc-L-alanine pentafluorophenyl ester

Aims: The present investigation is targeted towards the synthesis of a novel analogue of a natural peptide of marine origin. Background: Marine sponges are enriched with bioactive secondary metabolites, especially circu-lar peptides. Heterocycles are established organic compounds with potential biological value. Tak-ing into consideration the bio-properties of heterocycles and marine sponge-derived natural pep-tides, an effort was made for the synthesis of a heterocyclic analogue of a natural cyclopeptide. Objective: A heterocyclic analogue of a sponge-derived proline-containing cyclic peptide, rolloam-ide A, was synthesized by interaction of Boc-protected L-histidinyl-L-prolyl-L-valine and L-prolyl-L-leucyl-L-prolyl-L-isoleucine methyl ester and compared with synthetic rolloamide A with bioac-tivity against bacteria, fungi, and earthworms. Methods: The synthesis of cycloheptapeptide was accomplished employing the liquid phase method. The larger peptide segment was prepared by interaction of Boc-protected L-prolyl-L-leu-cine with L-prolyl-L-isoleucine methyl ester. Similarly, the tripeptide unit was synthesized from Boc-protected L-histidinyl-L-proline with L-valine ester. The linear heptapeptide segment (7) was cyclized by utilizing pentafluorophenyl (pfp) ester, and the structure was elucidated by elemental and spectral (IR, 1H/13C NMR, MS) analysis. The peptide was also screened for diverse bioactivities such as antibacterial, antifungal, and potential against earthworms and cytotoxicity. Results: The novel cyclooligopeptide was synthesized with 84% yield by making use of car-bodiimides. The synthesized cyclopeptide exhibited significant cytotoxicity against two cell lines. In addition, promising antifungal and antihelmintic properties were observed for newly synthesized heterocyclic peptide derivative (8) against dermatophytes and three earthworm species at 6 μg/mL and 2 mg/mL, respectively. Conclusion: Solution-phase technique employing carbodiimide chemistry was established to be promising for synthesizing the cycloheptapeptide derivative (8), and C5H5N was proved to be a better base for heptapeptide circling when compared to N-methylmorpholine and triethylamine.

The utility of an electron-deficient, air stable, and commercially available Lewis acid tris(pentafluorophenyl)borane has recently been comprehensively explored. While being as reactive as its distant cousin boron trichloride, it has been shown to be much more stable and capable of catalyzing a variety of powerful transformations, even in the presence of water. The focus of this review will be to highlight those catalytic reactions that utilize a silane as a stoichiometric reductant in conjunction with tris(pentafluorophenyl) borane in the reduction of alcohols, carbonyls, or carbonyl-like derivatives.

Although the palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl esters has received significant attention, there is a lack of methods that utilize cheap and readily accessible Pd-phosphane catalysts, and can be routinely carried out with high cross-coupling selectivity. Herein, we report the first general method for the cross-coupling of pentafluorophenyl esters (pentafluorophenyl = pfp) by selective C⁻O acyl cleavage. The reaction proceeds efficiently using Pd(0)/phosphane catalyst systems. The unique characteristics of pentafluorophenyl esters are reflected in the fully selective cross-coupling vs. phenolic esters. Of broad synthetic interest, this report establishes pentafluorophenyl esters as new, highly reactive, bench-stable, economical, ester-based, electrophilic acylative reagents via acyl-metal intermediates. Mechanistic studies strongly support a unified reactivity scale of acyl electrophiles by C(O)⁻X (X = N, O) activation. The reactivity of pfp esters can be correlated with barriers to isomerization around the C(acyl)⁻O bond.