835896-95-2Relevant academic research and scientific papers
Linear fused pyran-dioxane-cyclohexane tricycles: Synthesis of the five linkage isomers and ensuing reactions
Lichtenthaler, Frieder W.,Cuny, Eckehard
, p. 4911 - 4920 (2004)
A systematic investigation of the mono-O-glycosylation of meso-, (S,S)-, and (R,R)-cyclohexane-1,2-diol with the D-glucose-derived 2-ketohexosyl bromide 5 is presented. In each instance, simple Koenigs-Knorr conditions not only elicit the exclusive formation of the respective β-2-ketoglycosides, but also effect their subsequent intramolecular hemiketalization to provide tricycles with a 1,5,10-trioxa-perhydroanthracene framework. The linkage geometries of the products - two each from the meso- (→ 10, 12) and (S,S)-diols (→ 16, 17), and only one from the (R,R)-isomer (→ 26) - are determined in the hemiketalization step by an interplay of the anomeric effect and steric factors, favoring those isomers in which the pyran ring oxygen and the ketal-OH are in a trans-diaxial disposition. The most propitious case with respect to uniformity of reaction and yield (87%) turned out to the (R,R)-diol-derived cis-cisoid-trans-fused 26 as steric and stereoelectronic factors operate concertedly in the hemiketalization step. In each of these pyran-dioxane-cyclohexane tricycles, the acetalic hydroxyl group could be removed by BF3-mediated reduction with triethylsilane, the 1H NMR spectroscopic data of the respective products 14, 15, 18 and 28 being instrumental in assigning their linkage geometries. Slightly basic conditions (nBu4NOAc in acetonitrile) elicit highly stereoselective rearrangements in the pyran ring, for example 16 → 23 and 26 → 30; the tricycles have the structurally and stereochemically correct framework of a variety of cardenolides, in which a 2-ketosugar is doubly linked to a steroidal aglycon-diol. Thus, the methodology elaborated here shows high promise to provide a first, preparatively satisfactory access to this type of cardiac glycosides as well as to spectinomycin type antibiotics. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
