A norbornyl route to aminocyclohexitols: syntheses of diverse aminocarbasugars and 'confused' aminocarbasugars

New syntheses of a range of aminocyclitols, of the aminocarbasugar and 'confused' aminocarbasugar type, from simple, readily available norbornyl derived building-blocks is reported. Our synthetic approaches incorporate features that provide for large product diversity in terms of the placement of the amino group on the cyclohexitol matrix

Use of the Exciton Chirality Method in the Investigation of the Ligand Gating of Synthetic Ion Channels

The objective of this brief highlight is to point out the central role of the exciton chirality method to gain insights on the structural basis of the recently achieved ligand gating of synthetic ion channels. This unprecedented ligand gating was achieved with an equally unprecedented transmembrane rigid-rod pi-stack architecture that is designed to adopt a closed conformation with helically stacked naphthalenediimide (NDI) acceptors. The intercalation of the complementary electron-rich dialkoxynaphthalene ligands then stimulates the untwisting of the closed pi-helices into hollow barrel-stave supramolecules. During this helix-barrel transition, the angle between the transition moments of the exciton-coupled NDI chromophores decreases toward zero. The corresponding disappearance of the split CD provides, according to the exciton chirality method, the otherwise elusive experimental support that ligand-gated ion channel formation really occurs by this rationally designed helix-barrel transition

Fluorometric Detection of Enzyme Activity with Synthetic Supramolecular Pores

The reversible blockage of synthetic pores formed by rigid-rod beta barrels, either by substrates or products, was used to sense a variety of enzymatic reactions in high-throughput format with "naked-eye" fluorescent detection. Improvement of sensor sensitivity beyond three orders of magnitude by straightforward internal mutations underscores the functional plasticity of rigid-rod beta barrels. Such detectors of enzyme activity with the aforementioned characteristics are needed in areas as diverse as proteomics and environmentally benign organic synthesis

A norbornyl route to aminocyclohexitols: syntheses of diverse aminocarbasugars and ‘confused’ aminocarbasugars

New syntheses of a range of aminocyclitols, of the aminocarbasugar and ‘confused’ aminocarbasugar type, from simple, readily available norbornyl derived building-blocks is reported. Our synthetic approaches incorporate features that provide for large product diversity in terms of the placement of the amino group on the cyclohexitol matrix

A general norbornyl based synthetic approach to carbasugars and ‘confused’ carbasugars

The norbornyl system has been recognized simply as a ‘locked’ carbasugar and a short, general approach to carbasugars and their new siblings, ‘confused’ carbasugars, from readily available 7-ketonorbornanes is reported

Catalytic Rigid-Rod β-Barrels with Hydrazide Cofactors to Convert Poor Substrates as Hydrazone Conjugates

The usefulness of pyrene-1,3,6-trisulfonates as cofactors for p-octiphenyl ?-barrel ion channels to mediate recognition and conversion of otherwise inaccessible benzaldehyde substrates is described

Stereoselective Synthesis of (2<i>S</i>,3<i>R</i>)‑α-Hydroxy-β-Amino Acids (AHBAs): Valinoctin A, (2<i>S</i>,3<i>R</i>)‑3-Amino-2-Hydroxydecanoic Acid, and a Fluorescent-Labeled (2<i>S</i>,3<i>R</i>)‑AHBA

We report the stereoselective synthesis of an alkynyl side-chain containing (2<i>S</i>,3<i>R</i>)-α-hydroxy-β-amino acid ((2<i>S</i>,3<i>R</i>)-AHBA) analogues. The Cu­(I)-catalyzed reactions of (<i>R</i>)-glyceraldehyde acetonide and dibenzylamine with terminal alkynes provided the corresponding (2<i>S</i>,3<i>R</i>)-α-amino alcohols with good-to-excellent diastereoselectivity. Subsequent chemical transformations provided easy access to the alkynyl side-chain containing (2<i>S</i>,3<i>R</i>)-AHBAs. The utility of the methodology was demonstrated by the stereoselective synthesis of valinoctin A and (2<i>S</i>,3<i>R</i>)-3-amino-2-hydroxy­decanoic acid ((2<i>S</i>,3<i>R</i>)-AHDA). Photophysical properties and cell permeability of a pyrene-labeled (2<i>S</i>,3<i>R</i>)-AHBA were also determined

Stereoselective Synthesis of (2<i>S</i>,3<i>R</i>)‑α-Hydroxy-β-Amino Acids (AHBAs): Valinoctin A, (2<i>S</i>,3<i>R</i>)‑3-Amino-2-Hydroxydecanoic Acid, and a Fluorescent-Labeled (2<i>S</i>,3<i>R</i>)‑AHBA

We report the stereoselective synthesis of an alkynyl side-chain containing (2<i>S</i>,3<i>R</i>)-α-hydroxy-β-amino acid ((2<i>S</i>,3<i>R</i>)-AHBA) analogues. The Cu­(I)-catalyzed reactions of (<i>R</i>)-glyceraldehyde acetonide and dibenzylamine with terminal alkynes provided the corresponding (2<i>S</i>,3<i>R</i>)-α-amino alcohols with good-to-excellent diastereoselectivity. Subsequent chemical transformations provided easy access to the alkynyl side-chain containing (2<i>S</i>,3<i>R</i>)-AHBAs. The utility of the methodology was demonstrated by the stereoselective synthesis of valinoctin A and (2<i>S</i>,3<i>R</i>)-3-amino-2-hydroxy­decanoic acid ((2<i>S</i>,3<i>R</i>)-AHDA). Photophysical properties and cell permeability of a pyrene-labeled (2<i>S</i>,3<i>R</i>)-AHBA were also determined

Conformationally restricted Nucleocyclitols: a study into their conformational preferences and supramolecular architecture in the solid state

With the intent of probing the feasibility of employing annulation as a tactic to engender axial rich conformations in nucleoside analogues, two adenine-derived, "conformationally restricted" nucleocylitols, 9 and 10, have been conceptualized as representatives of a hitherto unexplored class of nucleic acid base-cyclitol hybrids. A general synthetic strategy, with an inherent scope for diversification, allowed rapid functionalization of indane and tetralin to furnish 9 and 10 respectively in fair yield. Single-crystal X-ray diffraction analysis revealed that the two nucleocyclitols under study, though homologous, present completely dissimilar modes of molecular packing, marked, in particular, by the nature of involvement of the adenynyl NH2 group in the supramolecular assembly. In addition, the crystal structures of 9 and 10 also exhibit two different conformations of the functionalized cyclohexane ring. Thus, while the six-membered carbocycle in cyclopenta-annulated 9 exists in the expected chair (C) conformation that in cyclohexaannulated 10, which crystallizes as a dihydrate, shows an unusual twist-boat (TB) conformation. From a close analysis of the 1HNMR spectroscopic data recorded for 9 and 10 in CD3OD, it was possible to put forth a putative explanation for the uncanny conformational preferences of crystalline 9 and 10

Conformationally Restricted Nucleocyclitols: a Study into their Conformational Preferences and Supramolecular Architecture in the Solid State

With the intent of probing the feasibility of employing annulation as a tactic to engender axial rich conformations in nucleoside analogues, two adenine-derived, ``conformationally restricted'' nucleocylitols, 9 and 10, have been conceptualized as representatives of a hitherto unexplored class of nucleic acid base-cyclitol hybrids. A general synthetic strategy, with an inherent scope for diversification, allowed rapid functionalization of indane and tetralin to furnish 9 and 10 respectively in fair yield. Single-crystal X-ray diffraction analysis revealed that the two nucleocyclitols under study, though homologous, present completely dissimilar modes of molecular packing, marked, in particular, by the nature of involvement of the adenynyl NH2 group in the supramolecular assembly. In addition, the crystal structures of 9 and 10 also exhibit two different conformations of the functionalized cyclohexane ring. Thus, while the six-membered carbocycle in cyclopenta-annulated 9 exists in the expected chair (C) conformation that in cyclohexaannulated 10, which crystallizes as a dihydrate, shows an unusual twist-boat (TB) conformation. From a close analysis of the (HNMR)-H-1 spectroscopic data recorded for 9 and 10 in CD3OD, it was possible to put forth a putative explanation for the uncanny conformational preferences of crystalline 9 and 10