A formal, one-pot, [4+4] cyclization pathway for the generation of 8-member sultams via in-situ generation of an ortho-quinone methide (o-QM) is reported. The pairing of ambiphilic synthons in a complementary fashion is examined whereby o-fluorobenzenesulfonamides are merged with insitu-generated o-QM in a formal [4+4] cyclization pathway to afford 5,2,1-dibenzooxathiazocine-2,2-dioxide scaffolds under microwave (mW) conditions. The method reported represents the first use of an o-QM in a formal hetero [4+4] cyclization.The development of chemical methodologies allowing ready access to novel heterocyclic scaffolds in a minimal number of steps is a key facet of drug discovery. Single pot, multicomponent reaction (MCR) strategies in particular have gained high value in this regard. 1 The great majority of these reactions involve the combination of reactive partners possessing single nucleophile-electrophile interactions, followed by subsequent merging in domino, cascade or tandem pathways to produce heterocyclic moieties. In comparison, synthons containing both electrophilic and nucleophilic sites (ambiphilic synthons) 2,3,4 have great potential in developing new reaction pathways with high step economy, 5 but remain underdeveloped. Interest in the development of chemical methodologies for the production of diverse sultam libraries has led to the exploration of complementary ambiphile pairing (CAP) pathways as part of a general strategy for the production of benzofused sultams in a facile manner ( Figure 1).At the heart of the titled method is the complementary pairing of two ambiphilic synthons, ofluoro benzenesulfonamides and ortho-quinone methide (o-QM) in a formal one-pot [4+4] approach to afford the novel 5,2,1-dibenzooxathiazocine-2,2-dioxide ring system. This route augments a recently reported [4+3] epoxide cascade strategy developed in our laboratory and others using the ambiphilic character of o-fluorobenzenesulfonamides for the synthesis of benzofused sultams. 6 phanson@ku.edu. Supporting Information Available: Experimental details and spectral charactization for all compounds. This material is available free of charge via the Internet at http://pubs.acs.org. The aforementioned dibenzooxathiazocine ring system represents a new subclass within sultams that have not been reported to-date. Sultams are a class of non-natural heterocycles that have gained prominence in recent years due to their activity against a wide spectrum of biological targets. 12,13 Their acyclic precursors, sulfonamides, are highly versatile synthons due to the tunability of the SO 2 NH pKa. 14 In this regard, o-fluorobenzene sulfonamides are particularly attractive due to the highly electron withdrawing nature of the SO 2 functionality, in conjunction with the o-fluoro substituent, which impart enhanced electrophilicity at the ortho-carbon as well as attenuated acidity/nucleophilicity of the sulfonamide NH ( Investigations commenced with the production of an array of 2° o-fluorobenzenesulfonamides under modified Schotten-Bau...
Herein we report a facile transformation of hydroxylated cucurbit[n]uril (CB[n], n = 6 and 7) to other functionality-conjugated CB[n]s by nucleophilic substitution of the hydroxyl group with a wide range of nitriles and alcohols. The reaction proceeds efficiently via generation of a superelectrophilic carbocation on the CB framework from hydroxylated CB[n]s under superacidic conditions. One of the resulting CB[n] derivatives with reactive functionality, monocarboxylated CB[7], is efficiently conjugated to an enzyme (horseradish peroxidase, HRP) by amide coupling. This provides a CB[7]conjugated functional biomaterial (CB[7]-HRP) that selectively detects proteins labeled with a guest, adamantylammonium (AdA), based on bioorthogonal high-affinity host−guest interactions between CB[7] and AdA. We demonstrated the potential of overcoming the limitations in preparing reactive functional CB[n] derivatives, enabling the exploration of novel bioapplications of CB[n]-based host−guest chemistry with new CB[n]-conjugated functional materials.
In this feature article, the two types (molecular amphiphile and supramolecular amphiphile) of CB-based amphiphiles, their self-assemblies and their applications for useful nanotherapeutics and theranostics are presented with future perspectives.
Hierarchical self‐assembly of building blocks over multiple length scales is ubiquitous in living organisms. Microtubules are one of the principal cellular components formed by hierarchical self‐assembly of nanometer‐sized tubulin heterodimers into protofilaments, which then associate to form micron‐length‐scale, multi‐stranded tubes. This peculiar biological process is now mimicked with a fully synthetic molecule, which forms a 1:1 host‐guest complex with cucurbit[7]uril as a globular building block, and then polymerizes into linear poly‐pseudorotaxanes that associate laterally with each other in a self‐shape‐complementary manner to form a tubular structure with a length over tens of micrometers. Molecular dynamic simulations suggest that the tubular assembly consists of eight poly‐pseudorotaxanes that wind together to form a 4.5 nm wide multi‐stranded tubule.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.