Template‐Directed Synthesis of an Inverted Spiro Architecture

Abstract

The regular bicyclic spiro motif is highly abundant given its synthetic accessibility while the diastereomer-virtually obtained through inversion at the central atom-is almost unknown. We have developed methodology to access the elusive inverted spiro architecture by employing a covalent template-directed approach. Comparison with the regular spiro bicycle analog unequivocally established the diastereomeric relationship, providing insight into the fascinating stereochemical and structural properties.

[2]Catenane Synthesis via Covalent Templating

“…This interaction is reduced in 9 a as the intra‐annular fragment limits the ability of the ketone macrocycle (in red) to fold. These findings are consistent with observations made on similar inverted spiro architectures previously synthesized via our backfolding approach [29, 35] …”

“…These findings are consistent with observations made on similari nverted spiro architectures previously synthesized via our backfolding approach. [29,35] Remarkably,s olvolysis of the ester linkages in 23 b gave intermediate 25 b' as as table compound at room temperature, which required extensive heating to unwind to the thermodynamically favored conformer 25 b.M olecular mechanicsm odeling of structures 25 b' and 25 a' suggest that the benzylic groups (in black) could hamper this process, as they barely fit in the macrocycle cavity according to space filling representations (see supporting information). However,s of ar we have no sound explanation for the exceptional differences in the kinetics of this step between 25 a' and 25 b'.From unwound macrocycle 25 b,t he trivial spiro bismacrocycle 26 b waso btained after RCM and catalytic hydrogenation.…”

Covalently Templated Syntheses of Mechanically Interlocked Molecules

“…Whereas a rigid fluorene moiety was used to ensure orthogonality in the synthesis of 25 and 27, we later showed that the backfolding strategy is compatible with a 'plain' central carbon atom linking four flexible alkyl chains (Scheme 7). 33 The temporary linkages in 28 again place the red ring precursors above and below the central carbon atom. This conformation guarantees the occurrence of backfolding cyclization to give diene 29.…”

Fluorescent Self‐Threaded Peptide Probes for Biological Imaging

“…[14,15] At present, the standard solution is to simply decorate the fluorophore structure with multiple charged functional groups [16] but this approach can be problematic because ahighly charged fluorescent label can alter as mall peptidestargeting properties. [17] Here we describe ac onceptually new way to create ad eep-red fluorescent peptide for high-performance bioimaging.The key design element is aself-threaded molecular Figure-eight architecture with ab uried fluorophore.T he literature contains asmall scattered collection of publications describing Figure-eight molecules, [18][19][20][21][22][23][24] and afew of them are self-threaded structures, [25][26][27] although none of the latter incorporate peptides or were designed for ap ractical application such as fluorescence imaging.T he buried fluorophore is as quaraine dye that exhibits narrow and intense deep-red absorption and emission bands (ex:6 40-660 nm, em:6 60-680 nm). [28,29] More than adecade ago we discovered that the chemical and fluorescence properties of aw ater-soluble squaraine dye can be greatly enhanced by encapsulating the dye within ap rotective tetralactam macrocycle and creating am echanically interlocked squaraine rotaxane.…”