Heterocyclic pentafluorophenyl sulfonate esters as shelf stable alternatives to sulfonyl chlorides

Heterocyclic pentafluorophenyl sulfonate esters are shelf stable alternatives to the often less stable sulfonyl chlorides. They are easily prepared from thiols and react readily with primary and secondary amines to produce sulfonamides in high yields.     

Electrophilic polyfluoroalkylating agents based on sulfonate esters

This review surveys selected electrophilic polyfluoroalkylating reagents, polyfluoroalkyl alkane- and arenesulfonates, that have been used for the introduction of longer perfluorinated chains (C_nF_2n+1; n ≥ 4) with methylene, ethylene or propylene spacers into the substrate. Polyfluoroalkyl mesylates, tosylates, triflates and nonaflates are described with their applications in various syntheses of polyfluorinated compounds.     

Resolution of pentafluorophenyl esters using oxazolidin-2-ones

A series of structurally related racemic pentafluorophenyl active esters were resolved using an equimolar amount of (S)-4-phenyloxazolidin-2-one. The levels of diastereocontrol were found to be excellent (80-96% de) at ∼40% conversion.     

Sequential conversion of orthogonally functionalized diblock copolymers based on pentafluorophenyl esters

Statistic and block copolymers exhibiting activated ester side groups were synthesized by reversible addition‐fragmentation chain transfer polymerization in the presence of cumyl dithiobenzoate, benzyl dithiobenzoate, and 4‐cyano‐4‐((thiobenzoyl)sulfanyl)pentanoic acid as chain transfer agents. Pentafluorophenyl methacrylate and pentafluorophenyl 4‐vinylbenzoate were used to enable a sequential functionalization of the obtained copolymers by conversion of the activated esters with different amines. ¹H NMR spectroscopy, ¹⁹F NMR spectroscopy, and FTIR spectroscopy showed the successful step‐by‐step conversion of the different activated esters by aniline followed by aliphatic amines, thereby realizing a sequential functionalization of block copolymers with just one specific reactive group. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3683–3692, 2010     

药物中磺酸酯类基因毒性杂质研究进展

该文概述了近10年来有关药物中基因毒性杂质监管指南的完善历程与相关检测方法的研究进展。介绍了基因毒性杂质从早期的完全避免到目前的阶段化毒理学关注阈值（TTC）的风险控制理念以及各主流监管机构的具体要求。作为一类重要的基因毒性杂质,磺酸酯主要来源于磺酸及衍生物与低级醇（如甲醇、乙醇、异丙醇等）之间发生的副反应,具有化学结构类型多样化的特点。该文较为详尽地介绍了磺酸酯的形成机理和文献所采用的液相色谱法和气相色谱法,并对色谱方法的选择、预处理方式、衍生化方法及相应痕量水平的灵敏度和回收率等进行了评述。由此期望为合理控制药物中磺酸酯类基因毒性杂质,为保证药物的质量安全性提供有益的指导意见。     

Use of pentafluorophenyl esters in the synthesis of intermediate fragments of ACTH

The results are given of the synthesis of the heptapeptide 13–19 of the natural sequence of ACTH using, in a number of stages, the pentafluorophyl esters of amino acids and peptides in combination with the temporary silyl protection of the carboxy group of the amino components. The intermediate compounds were obtained with good yields (70–90%) in chromatographically homogeneous form and their physicochemical characteristics did not differ from those of similar products obtained by other methods and described in the literature. The identification and checking of the purity of the compounds synthesized was carried out not only by traditional methods but also by the¹³C NMR method and by high-pressure liquid chromatography. Some physicochemical characteristics of the compounds synthesized are given.     

Synthesis of pentafluorophenyl esters from acid fluorides and potassium pentafluorophenoxide

The reaction of potassium pentafluorophenoxide with acid fluorides has been investigated and found to yield pentafluorophenyl esters. The compounds CH₃C(O)OC₆F₅, CF₃C(O)OC₆F₅, CF(O)OC₆F₅, CF₃OOC(O)OC₆F₅, and (C₆F₅O)₂CO have been prepared. Physical and spectral data for each compound are reported.     

Reduction of pentafluorophenyl esters to the corresponding primary alcohols using sodium borohydride

Primary alcohols and chiral N-protected 2-amino alcohols can be obtained in high yields from the reaction of pentafluorophenyl esters of the corresponding carboxylic acids with sodium borohydride in THF under mild conditions. This reductive method is rapid and compatible with various functional groups as well as with the most common N-protective groups Z, Boc and Fmoc.     

Sulfonamide synthesis using N-hydroxybenzotriazole sulfonate: an alternative to pentafluorophenyl (PFP) and trichlorophenyl (TCP) esters of sulfonic acids

The N-hydroxybenzotriazole (HOBt) sulfonate esters undergo amidation under ambient conditions in the presence of di-isopropylethyl amine. This method can be applied to varieties of amines including sterically hindered amino acid esters in less time with reasonably good yields.HOBt ester of sulfonic acids can be a replacement for pentafluorophenyl and trichlorophenyl ester as well as chloride moiety of sulfonyl chloride for amidation.     

Pentafluorophenyl sulfonate ester as a protecting group for the preparation of biaryl- and heterobiaryl sulfonate esters

The use of the pentafluorophenyl (PFP) group as a sulfonic acid protecting group has allowed the synthesis of new biaryl- and heterobiaryl-PFP-sulfonate esters by use of the Suzuki-Miyaura reaction. The successful employment of a novel inorganic base, anhydrous sodium tetraborate, was crucial to give the products in excellent yields. The PFP-sulfonate ester has been previously shown to be an excellent alternative to sulfonyl chlorides in the synthesis of sulfonamides. [structure: see text]     

Synthesis of near-IR fluorescent oxazine dyes with esterase-labile sulfonate esters

Near-IR oxazine dyes are reported that contain sulfonate esters which are rapidly cleaved by esterase activity to unmask highly polar anionic sulfonates. Strategies for the synthesis of these dyes included the development of milder dye condensation conditions with improved functional compatibility and the use of an alkyl halide that allows for the introduction of esterase-labile sulfonates without the need for sulfonation of the target molecule.     

Observations on the reactivity of tris(tetramethylethylenedioxyboryl)methide ion

Treatment of tetrakis(tetramethylethylenedioxyboryl)methane, (Me₄C₂ - O₂B)₄C, in THF with butyllithium at ?78° generates the tris(tetramethylethylenedioxyboryl)methide ion, (Me₄C₂O₂B)₃C^?, which reacts with chlorotrimethylsilane at ?78° to form trichlorosilyltris(tetramethylethylenedioxyboryl)-methane, (Me₄C₂O₂B)₃CSiMe₃. The yield was low, but other attempts to form silyltriborylmethanes have failed altogether. The ion (Me₄C₂O₂B)₃C^? reacts with tetraphenylcyclopentadienone at ?78° to form the expected fulvene, 1,1-bis-(tetramethylethylenedioxyboryl)-2,3,4,5-tetraphenylfulvene. The red color of the tetraphenylcyclopentadienone is converted immediately to the brown of the fulvene product, indicating that the β-elimination of boron and oxygen occurs rapidly under basic conditions at ?78°.     

Direct synthesis of sulfonamides and activated sulfonate esters from sulfonic acids

A general new method for the preparation of sulfonamides and activated sulfonate esters by the direct coupling of sulfonic acid salts with amines and alcohols using the reagent triphenylphosphine ditriflate is described. A new reusable polymer-supported reagent for these transformations under heterogeneous conditions is also described. These methods provide a fundamentally new approach to making small molecules containing the sulfonamide functional group.     

Oxetane synthesis via cyclisation of aryl sulfonate esters on polystyrene and PEG polymeric supports

The addition of suitably protected pentaerythritols to polymer supported sulfonyl chloride with subsequent alkoxide formation and intramolecular cyclisation to generate oxetanes is described. This convenient method for the preparation of oxetanes has several advantages over analogous solution phase reactions and the methodology is extended to the preparation and use of a novel PEG-sulfonyl chloride.     

Synthesis and reactivity of sulfonamides containing boronate esters

Sulfonamides containing pinacol protected boronate ester groups have been prepared by the addition of H₂NC₆H₄Bpin (pin = O₂C₂Me₄) to sulfonyl chlorides p‐RC₆H₄SO₂Cl (R = CH₃, NO₂). Hydrogenation of the nitro derivatives afford the corresponding sulfanilamides without compromising the aryl‐Bpin bond. The sulfanilamides were further functionalized to afford novel platinum complexes containing boranosulfonamides. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:369–375, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20025