Quest for inosito-inositols: synthesis of novel, annulated and conformationally locked inositols

Abstract

A new family of annulated inositols (inosito-inositols) has been conceptualized. Naphthalene has been elaborated into novel cyclohexa-annulated neo-and chiro-inositols, with two additional hydroxyl functionalities, through a series of stereoselective oxyfunctionalization protocols. The trans-ring fusion present in these new annulated inositols ensures conformational locking.

Diverse and Yet Unified: A Comparative Study of the Supramolecular Assemblies of Three Diastereomeric Perhydro‐2,3,4a,6,7,8a‐naphthalenehexols

“…[5] syn-Diol 9, obtained upon regioselective dihydroxylation of 7 at low temperature, formed the starting material for the synthesis of hexol 5. [6] Exhaustive epoxidation of 9 with m-CPBA, followed by mild acid-catalyzed ring opening in the mixture of diepoxides thus obtained, afforded 5 as a single diastereomer. In order to facilitate purification of polar hexol 5, the latter was first converted into tetraacetate 10, from which polyol 5 was regenerated almost quantitatively through base-catalyzed transesterification (Scheme 2).…”

“…Reagents and conditions: (a) Ref. [6] ; (b) m-CPBA, CH 2 Cl 2 , room temp., 3 h; (c) (i) 10 % AcOH (aq. ), 55°C, 4 h; (ii) Ac 2 O, DMAP, room temp., 6 h, 75 % over steps (b) and (c); (d) K 2 CO 3 , MeOH, room temp., 6 h, quant.…”

A New Glucose: Towards Conformationally Locked Hexoses through Annulation

“…Scheme 2 shows a generalized representation of this simple tactic for accessing annulated hexoses 9a-d from the corresponding bicyclic allylic alcohols 18-21, with ozonolysis planned to serve as the pivotal step to set up the cascade intramolecular acetalization. Acquisition of precursors 18-21 thus became our primary concern, and for this purpose the readily available and recently reported trans-CHD 8 [7] was identified as an appropriate starting point.…”

“…[7] While the natural myo-inositol 3, for example, exits in a stable conformation with five of its hydroxy groups in equatorial dispositions (5eq/1ax), the cyclohexane-annulated myo-inositol 4 has been shown to exist in a locked conformation with a five axial/one equatorial (5ax/1eq) disposition of its hydroxy groups ( Figure 1). Furthermore, the carbocyclic annulus in 1 and 2 serves as a handle with which to fine-tune the hydrophobicity of the polar inositols and to achieve chemodifferentiation of the hydroxy groups.…”

“…The synthesis of bicyclic inositols 1-2 began from simple, commercially available aromatics such as indane (5) and tetralin (6) through the intermediacy of annulated trans-cyclohexadiene diol (trans-CHD) derivatives 7 and 8, respectively (Scheme 1). [7] These interesting efforts in the inositol area impelled us to extend the strategy of carbocyclic annulation to provide conformationally locked carbohydrates. Consequently, a new family of annulated carbohydrates 9a-d functioning as new sugar variants was conceptualized (Figure 2).…”