Polycyclitols: novel conduritol and carbasugar hybrids as a new class of potent glycosidase inhibitors

We have conceptualized new molecular entities (bicyclitols) in which two conduritol and two carbasugar moieties are embedded in a polyhydroxylated decahydronaphthalene framework and achieved their syntheses in a stereo- and regioselective manner. One of the bicyclitols was found to be a potent and selective α -glucosidase inhibitor

Enantioselective total synthesis of (+)-Panepophenanthrin, a novel inhibitor of the Ubiquitin-activating enzyme

An enantioselective total synthesis of the novel natural product (+)-panepophenanthrin has been accomplished in which a biomimetic Diels-Alder dimerisation is a key step. The monomeric precursor 2 was assembled from the readily available Diels-Alder adduct of cyclopentadiene and p-benzoquinone through a short, simple sequence employing chemo- and stereoselective operations

Novel conformationally locked inositols: from aromatics to annulated cyclitols

A new family of ring-annulated inositols with "locked" conformations has been designed to deliver a range of these biologically important entities in "unnatural conformations" while retaining their "natural configurations". The simple "tool" of trans ring fusion has been used to "lock" the conformation of the annulated inositols. Short, simple syntheses of a range of these novel cyclitols have been achieved from readily available aromatic precursors such as tetralin and indane. Along the way, annulated C2-symmetric cyclohexadiene-trans-diol (trans-CHD) derivatives have been prepared for the first time and serve as the pivotal building blocks for generating the oxy-functionalization pattern of inositols. The presence of chemo-differentiated hydroxyl groups in our novel inositols is expected to facilitate the installation of phosphate diversity to harness the biological potential of these entities

Enantioselective total synthesis of polyoxygenated cyclohexanoids: (+)-streptol, ent-RKTS-33 and putative '(+)-parasitenone'. identity of parasitenone with (+)-epoxydon

Short, simple and enantioselective syntheses of the natural product (+)-streptol, the non-peptide apoptosis inhibitor ent-RKTS-33 and the putative structure of 'parasitenone' have been accomplished from the readily available chiral building block. 'Parasitenone' has been shown to be identical with the known natural product epoxydon

RhCl3/amine-catalyzed [2+2+2] cyclization of alkynes

The RhCl3-3H(2)O/i-Pr2NEt-catalyzed [2+2+2] cyclotrimerization of alkynes has been achieved. The reaction can be widely used for various alkynes and provides tri- OF hexa-substituted benzenes regioselectively in high yields. The [2+2+2] cycloaddition of diynes and alkynes is also developed, and it affords benzene derivatives in moderate to high yields.</p

Polycyclitols: synthesis of novel carbasugar and conduritol analogues as potential glycosidase inhibitors

Stereoselective syntheses of a new family of hydrindane based bicyclitols with seven hydroxyl groups in a diverse stereochemical array have been accomplished from readily available building-blocks. One of the bicyclitols 12 has been found to exhibit moderate a-glucosidase inhibitory activity in enzymatic assays

Polycyclitols: novel conduritol and carbasugar hybrids as new glycosidase inhibitors

A family of novel carbasugar analogues (bicyclitols) based on cis-hydrindane and cis-decalin frameworks has been conceptualized. These novel entities can be regarded as conduritol and carbasugar hybrids. Syntheses of these polyhydroxylated entities have been achieved in stereo- and regioselective manners, starting from the readily available Diels-Alder adducts of 5,5-dimethoxy-1,2,3,4-tetrachlorocyclopentadiene and appropriate dienophiles like cyclopentadiene or p-benzoquinone, that embody a masked 7-ketonorbornenone moiety. Thermally induced chelotropic elimination of CO from the appropriately functionalized 7-ketonorbornenone derivatives to deliver annulated bicyclic 1,3-cyclohexadiene derivatives was the key step in this synthetic endeavor. Further oxy-functionalization of the 1,3-cyclohexadiene moiety delivered the targeted polycyclitols. A preliminary investigation of the glycosidase inhibitory potency of these bicyclitols, identified compounds 18 and 54 as potent and selective inhibitors of α-glucosidase (yeast)

A new glucose: towards conformationally locked hexoses through annulation

A new family of surface-modified carbohydrates with locked, axial-rich conformations and bipolarofacial architectures has been developed with the aid of carbocyclic ring annulation. These novel trans-decalin-based carbohydrates have been synthesized, from simple aromatic precursors such as tetralin, through the ozonolysis of an appropriately protected allylic alcohol, followed by a cascade of intramolecular acetalizations to generate the sugar pyran moiety. The stereoselective synthesis of (racemic) cyclohexane-annulated β-glucopyranoside and α -glucofuranoside from a common annulated trans-cyclohexadiene diol (trans-CHD) precursor underscores the versatility of our approach. The efficacy of the annulation stratagem in generating carbohydrate diversity has been demonstrated through the synthesis of two regioisomeric annulated gulose derivatives, which differ only in the site of ring annulation on the sugar moiety. The mapping of the MLP surface and solid-state architecture of the new sugar shows that cycloalkane annulation results in surface modification and fine-tuning of sugar hydrophilicity

Crystal structures of conformationally locked cyclitols: an analysis of hydrogen-bonded architectures and their implications in crystal engineering

A qualitative study has been carried out on selected polycyclitols to evaluate the potential of conformational locking of hydroxy groups in lending predictability to the O-H···O hydrogen-bonding network observed in the crystal structures of such compounds. The polycyclitols employed in this study are conformationally locked with all the hydroxy groups destined to be axial owing to the trans ring fusion(s) in the polycyclic carbon framework. The consequent formation of intramolecular O-H···O hydrogen bonds between the 1,3-syn diaxial hydroxy groups now permits any packing pattern in the polycyclitols to be described in terms of a small group of intramolecularly bonded molecular motifs linked to their respective neighbors by four O-H···O bonds. By using this model and the results of CSD analyses of polyols as a guide, the O-H···O hydrogen-bonded packing motifs most likely to be observed in the crystal structure of each polycyclitol were proposed and compared with those obtained experimentally

Polycyclitols: synthesis of novel carbasugar and conduritol analogues as potential glycosidase inhibitors

Stereoselective syntheses of a new family of hydrindane based bicyclitols with seven hydroxyl groups in a diverse stereochemical array have been accomplished from readily available building-blocks. One of the bicyclitols 12 has been found to exhibit moderate a-glucosidase inhibitory activity in enzymatic assays