Jonathan D. Wilden

Trichlorophenol (TCP) sulfonate esters: A selective alternative to pentafluorophenol (PFP) esters and sulfonyl chlorides for the preparation of sulfonamides

2,4,6-Trichlorophenol (TCP) sulfonate esters undergo effective aminolysis under conventional heating and microwave irradiation; the reactivity of these species is such that chemoselective transformations of PFP sulfonate esters can be achieved.

The sulfonamide motif as a synthetic tool

Sulfonamides are well known motifs in medicinal chemistry, forming a large family of antibacterial agents as well as being found in numerous other drugs. The chemistry of this functional group, however, is less well documented. This review seeks to bring together the various applications and advantages of this motif in organic synthesis, which includes the sulfonamide as an activating group, protecting group, leaving group and as a molecular scaffold.

A new approach to the pseudopterosins using an arene alkylation with a γ-methylene-γ-butyrolactone

A short and practical route to the tricyclic core of an unnatural pseudopterosin diastereoisomer is presented. Key features are an arene alkylation with a gamma -methylene-gamma -butyrolactone, viz. 10 --> 14, and an elaborate reduction sequence 14 --> 17 which both proceed diastereoselectively.

Transition-metal-free synthesis of aryl-substituted tert-butyl ynol ethers through addition/elimination substitution at an sp centre.

Nucleophilic attack of an alkoxide on an alkynyl sulfonamide leads to displacement of the sulfonamide at the sp centre and isolation of the ynol ether in good yield in a single operation. The mechanistic pathway has been probed by the use of coordinating additives, (13)C-labelling experiments and ab initio calculations, which indicated that an addition/elimination mechanism is in operation.

Transition-Metal-Free Synthesis of Ynol Ethers and Thioynol Ethers via Displacement at sp Centers: A Revised Mechanistic Pathway

We present here valuable extensions to our previous work in preparing highly functionalized, heteroatom-substituted alkynes via displacement at an sp center. Our results show that a wide range of ynol ethers can be prepared by the same methodology and that the same protocol can be applied to the synthesis of synthetically useful thioynol ethers. We also present new observations that have led us to revise our original hypothesis in favor of a pathway involving radical intermediates.

A versatile synthesis of 2,4-substituted oxazoles.

A variety of five-membered ring oxazoles have been synthesised with complete regiocontrol and without the requirement for ring oxidation via a reaction sequence based on a vinyl sulfonamide template.

Inhibition of dimethylarginine dimethylaminohydrolase (DDAH) and arginine deiminase (ADI) by pentafluorophenyl (PFP) sulfonates

A range of pentafluorophenyl (PFP) sulfonate esters derived from the reaction of PFP vinyl sulfonate and various nitrones are shown to have significant inhibitory activity against the bacterial enzymes DDAH and ADI.

Observations on the reactivity of pentafluorophenyl sulfonate esters

Studies on displacement reactions of alkyl pentafluorophenyl (PFP) sulfonates with amines are consistent with a mechanism involving an elimination-addition pathway; comparisons between the reactivity of PFP-sulfonates with sulfonyl chlorides and PFP-sulfonates with PFP-esters are also presented.

The Use of 3-Aminophthalimide as a Pro-Chemiluminescent Label in Chemiluminescence and Fluorescence-Based Cellular Assays

We present a labeling system for direct chemiluminescence-based cellular bioassays using the stable pro-chemiluminescent, luminol precursor, 3-aminophthalimide (API). API-coupled reporter molecules are detected chemiluminometrically after treatment with hydrazine, which converts the API label to luminol. API derivatives containing a variety of functional groups are readily synthesized, allowing for ease of coupling via the imide nitrogen to a host of reporter molecules. The fluorescent nature of APIs further allows for dual fluorescence and chemiluminescence studies. To highlight the utility of this label, we show that API-labeled insulin can be successfully utilized in cellular binding and transport assays and that an API-coupled mitochondrial probe (API-triphenylphosphonium(+)) can be used to both fluorescently and chemiluminometrically investigate mitochondrial function. We also assess the use of API as a polysaccharide and nucleic acid label, and we show that API-labeled palmitic acid undergoes cellular transport and lipid metabolism.