Go to page

Bibliographic Metadata

 The document is publicly available on the WWW


Cyclitols, polyhydroxylated five- and six-membered carbocycles, are isolated from natural sources as single compounds or as part of more complex structures and play key functions in biological systems. Especially during the last two decades, a new level of attention was focused on inositol phosphates after the discovery, in 1983, that myo-inositol-1,4,5-trisphosphate (Ins(1,4,5)P₃) is a Ca2+-mobilizing second messenger. In this work a de novo strategy for the preparation of inositol derivatives is presented. Starting from p-benzoquinone, optically pure compounds in both forms can be prepared easily via enzymatic resolution of derived diacetoxy conduritol B yielding the building blocks of this concept. In the first part, several myo-inositol phosphates were synthesized by use of either a C₂-symmetrical or a non-symmetrical approach. Among others, a new, very short and effective route to myo-Ins(1,3,4,5)P₄, myo-Ins(1,2,3,4,5)P₅, myo-Ins(1,2,4,5,6)P₅, myo-Ins(1,2,3,5,6)P₅ and myo-Ins(2,3,4,5,6)P₅ is presented. The second part further emphasizes the potential of this de novo approach in the construction of non-racemic inositol phosphate derivatives. The obtained azido-conduritols were transformed into several azido-myo-inositols on a multigram scale without the need for chromatographic separation. The described efficient, high-yielding routes allowed the introduction of nitrogen-containing functional groups in 1-, 3-, 4- and 6-position of the cyclitol ring system to give several pure azido- and amino-myo-inositols in both enantiomeric forms. In the third chapter a practical route is described for the preparation of a wide variety of enantiomerically pure inositol isomers. The potential of this concept is demonstrated by easy synthesis of myo-, L-chiro-, D-chiro-, scyllo-, epi-, allo- and neo-inositol derivatives. In the fourth chapter a new synthetic approach is described for the preparation of branched cyclitols from conduritol B by stereoselective hydroformylation, thereby extending the synthetic potential of the versatile building blocks by transforming them in two steps into carbasugar systems. To demonstrate the potential of this versatile approach Mycothiol, a GSH-similarity on inositolbasis, is synthesized by a new and diastereoselective access in the last chapter.