Conceptualization and Synthesis of the First Inosito‐Inositol (Decahydroxydecalin, DHD): In silico Binding to β‐Amyloid Protein

Abstract

Previously unknown entities in the form of 1,2,3,4,5,6,7,8,9,10‐decahydroxydecalins (DHDs) have been conceptualized and the first member of this class, an inosito‐inositol, has been synthesized from aromatic hydrocarbon naphthalene following a flexible strategy that is amenable to diversity creation. The DHD accessed here has been subjected to preliminary in silico evaluation with Aβ and may hold some promise in Alzheimer's disease therapeutics.

Polycyclitol derivatives restore long-term memory by regulating cdk5/p25 based tau signaling in experimental cerebral malaria

“…2. Our synthetic endeavour was envisioned from the diepoxide (13 ) which in turn was synthesized from commercially available naphthalene through a well-established reaction sequence (Rashid et al, 2020). Stereo-and regioselective opening of α-epoxide ring in (13 ) under mild acidic conditions led to epoxydiol ( 14).…”

Incisive analysis of hydrogen-bonded supramolecular architectures in designer polycyclitols: observation of some interesting self-assembly patterns

“…6 Recently, we and others have conceptualized polycyclitols as novel analogs of bioactive inositols displaying enhanced levels of hydroxyl functionalities with variegated stereochemical patterns and ring size variation to open up a new chemical space for supramolecular interactions and possible applications in biology and materials science. 7 Such constructs, harbouring multiple hydroxyl groups, contiguous or skipped are annulated inositols or polycyclitols, as displayed in Fig. 2.…”

“…8,9 An important example to recall is the promise shown by inositol derivatives in Alzheimer's disease and related neurodegenerative disorders. 7,10 As a part of our continuing interest in the area of polycyclitol design, 11 we got interested in the synthesis of a novel, hitherto unknown entity 1,2,3,4,5,6,7,8,9,10decahydroxydecalin 8, wherein each of the 10 carbon atoms of the cis-decalin backbone is embellished with a stereodefined hydroxy group, and our efforts in this quest have culminated in a successful first time attainment of the formidable objective. 7 During these travails, replete with inevitable meanderings enroute, we encountered several polyoxygenated cis-decalin based multifunctional intermediates bearing a combination of hydroxyl, epoxide, ether and cyclic carbonate groups in clearly defined regioand stereo-disposition.…”

“…8,9 An important example to recall is the promise shown by inositol derivatives in Alzheimer's disease and related neurodegenerative disorders. 7,10…”

“…As a part of our continuing interest in the area of polycyclitol design, 11 we got interested in the synthesis of a novel, hitherto unknown entity 1,2,3,4,5,6,7,8,9,10-decahydroxydecalin 8 , wherein each of the 10 carbon atoms of the cis -decalin backbone is embellished with a stereo-defined hydroxy group, and our efforts in this quest have culminated in a successful first time attainment of the formidable objective. 7 During these travails, replete with inevitable meanderings enroute, we encountered several polyoxygenated cis -decalin based multifunctional intermediates bearing a combination of hydroxyl, epoxide, ether and cyclic carbonate groups in clearly defined regio- and stereo-disposition. These highly oxygenated ensembles with interspersed hydroxyl groups on a decalin backbone were interesting in their own right and were tempting objects for closer structural scrutiny of their supramolecular architecture by X-ray crystallographic studies.…”