Enantioselective sulfonylation reactions mediated by a tetrapeptide catalyst

Abstract

While Nature excels at performing selective modifications of complex polyfunctional molecules through the use of tailoring enzymes, synthetic chemistry has lagged behind in this regard. In prior work, we have applied a biomimetic approach to this problem, developing small peptides to achieve various group transfer reactions on polyol substrates with high enantio- or regioselectivity. The utility of sulfonates as synthetic building blocks and the scarcity of direct, selective methods for their preparation prompted our investigation into this area. In this article we report the development of a π-methyl histidine-based tetrameric peptide that effects the desymmetrization of meso-1,3-diols through enantioselective (mono)sulfonylation. The catalyst exhibits structural similarities to another catalyst found to be effective in orthogonal group transfers, but results in modification of the enantiotopic alcohol. The practical and mechanistic implications of this discovery may extend beyond synthetic considerations and provide analogies to the diverse roles of histidine in enzyme active sites.

6. Experimental procedures for conducting organic reactions in continuous flow

“…Whereas small rigid organocatalysts offer only a limited number of sites for structural and functional diversity, peptides have a modular nature, which allows the creation of optimized catalysts. large number of peptidic catalysts have been designed [37], and it has been shown that N-terminal prolyl-peptides efficiently catalyze reactions proceeding via enamine intermediates [38]. Earlier, we reported the first continuous-flow approach for the selective asymmetric synthesis of -nitroaldehydes, utilizing solid supported peptidic catalysts readily synthesized and immobilized in a single step [39].…”

Trifunctional Organocatalysts: Catalytic Proficiency by Cooperative Activation

“…[47] Site-specific or spatially controlled sulfonation reactions are known to be mediated by tailoring enzymelike peptide catalysts. [48] Organocatalysis involving photons for completing SET cycles allows some specificity in catalysis initiation by utilising particular wavelengths in the UV/ Vis range. [49] In combination with host-guest chemistry, binding interactions can be spatially configured to localise organocatalytic events for enhanced catalytic proficiency.…”

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

“…46 This approach was also explored in reactions analogous to those catalyzed by kinases, culminating in the realization of peptide-catalyzed desymmetrizations of inositol derivatives (Figure 4C). 47–51 Here, two distinct peptide scaffolds are utilized to access different phosphorylated derivatives of 8 . These early reports of peptide-based nucleophilic catalysis helped establish a basis for the application of these concepts to the more complex substrates that are described below.…”