Stereoselective Synthesis of myo‐, neo‐, L‐chiro, D‐chiro, allo‐, scyllo‐, and epi‐Inositol Systems via Conduritols Prepared from p‐Benzoquinone

Abstract

A practical route is described for the flexible preparation of a wide variety of inositol stereoisomers and their polyphosphates. The potential of this approach is demonstrated by the synthesis of myo-, L-chiro-, D-chiro-, epi-, scyllo-, allo-, and neo-inositol systems. Optically pure compounds in either enantiomeric form can be prepared from p-benzoquinone via

Flexible Stereo‐ and Regioselective Synthesis of myo‐Inositol Phosphates(Part 1): Via Symmetrical Conduritol B Derivatives

“…Only distilled solvents were used. The building blocks (+)-and (-)-2, (-)-and (+)-3, and their precursors were prepared according to literature methods, [10,11] as were 1,4-di-O-benzylconduritol B (14) [12] and 1,4-bis(di-O-benzylphospho)conduritol B (17). [11] Purification and Analysis of Inositol Tris-and Tetrakisphosphates (HPLC-MDD): Inositol phosphates were purified and analyzed by the HPLC-MDD method described previously.…”

“…To this end (+)-14 was synthesized in a one-pot procedure in 70 % yield from diol (+)-2, as reported previously. [12] Subsequent acetylation of the free hydroxy groups gave (+)-15 (see Scheme 2). The diacetate (+)-3 could be converted in the same way into the enantiomer (-)-14.…”

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

“…[21] The important intermediate was the enantiomerically pure 63 that was used to prepare all the inositol derivatives apart from cis-and muco-inositols. p-Benzoquinone is inexpensive and the only starting material needed to prepare seven of the nine inositols in multigram quantities making this a diverse synthesis from one starting material.…”

Flexible Stereo‐ and Regioselective Synthesis of myo‐Inositol Phosphates(Part 2): Via Nonsymmetrical Conduritol B Derivatives

“…In view of the newly developed synthetic route to conduritol E and B derivatives, [22] it is possible to transform the bromohydrin derivative (+)-7 into diacetates via acetoxonium intermediates. This avoids epoxide formation and epoxide opening and thus prevents formation of the by-products mentioned above (see Scheme 3).…”

“…The two hydroxy groups were differentiated by monofunctionalization of the axial hydroxy group of 17 by a previously reported method. [22] Treatment of 17 with triethyl orthoacetate in anhydrous tetrahydrofuran under acidic conditions (p-toluenesulfonic acid) resulted in the formation of an intermediate orthoester that can be converted directly, with acetic acid, into the axial acetate. [27] Regioselectivity in this reaction can be traced to stereoelectronic effects.…”