Exploiting Differences in Solution vs Solid-Supported Reactivity for the Synthesis of Sulfonic Acid Derivatives

Abstract

We describe a method herein for the protection of aryl and alkyl sulfonates during synthesis which employs commercially available Wang or MBOH resin, both of which terminate as benzyl alcohols, as both a protecting group and "traceless" linker. Given the known instability of benzylic sulfonate esters to nucleophilic displacement in solution, this linkage is surprisingly stable: no loss of either aryl or alkyl sulfonates is observed when the resin is exposed to a wide variety of organic bases and solvents at room temperature. Further elaboration of the resin-bound sulfonates via Suzuki coupling is also described.

Trichloroethyl Group As a Protecting Group for Sulfonates and Its Application to the Synthesis of a Disulfonate Analog of the Tyrosine Sulfated PSGL-143−50 Peptide

“…The HPLC chromatogram of the crude peptide consisted of one major peak plus a few minor peaks . The − ESI mass spectrum of the crude peptide indicated that the major product in the crude mixture was desired TCE-protected peptide Ac-Ala-Thr-Glu-Phe( p -CH 2 SO 3 TCE)-Glu-Phe( p -CH 2 SO 3 TCE)-Leu-Asp-NH 2 ( 16 ) and no peaks corresponding to peptides that had undergone substitution of the TCE group with 2-MP were detected . After subjecting crude peptide 16 to H 2 (balloon), 30 wt.…”

Synthesis of Sulfonic Acid Salts and Sulfonic Acids by Advanced Cross‐Coupling Reaction of Vinyl Sulfonates

“…Direct cross‐coupling reactions of sulfonic acids are rare and non‐general, [6] which may be due to their ability to undergo desulfonylation at room temperature during cross‐coupling reactions [7] . The side chain modification of sulfonates by means of cross‐coupling reactions followed by the hydrolysis of sulfonates into sulfonic acids is feasible (Scheme 1b) [8] …”

“…[7] The side chain modification of sulfonates by means of cross-coupling reactions followed by the hydrolysis of sulfonates into sulfonic acids is feasible (Scheme 1b). [8] On the other hand, the formation of a CÀ C bond by means of cross-coupling reactions has become an indispensable tool for the synthesis of various molecules. [9] Despite the existence of both oxidative [10] and reductive [11] cross-coupling reactions, the CÀ C bond is often formed by the reaction between electrophilic and nucleophilic reagents.…”

PEG-related polymer resins as synthetic supports

“…Merrifield et al first developed the concept of solid-phase peptide synthesis [2-7] by using heterogeneous chloromethylated polystyrene that was lightly crosslinked with divinylbenzene (Merrifield resin, Figure 1(a)) in a wide range of synthetic methodologies [8][9][10][11][12][13]. Since then the use of polymers in various ways to facilitate synthesis and product purification has become widespread.…”