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Linear Fused Pyran‐Dioxane‐Cyclohexane Tricycles: Synthesis of the Five Linkage Isomers and Ensuing Reactions
Author(s) -
Lichtenthaler Frieder W.,
Cuny Eckehard
Publication year - 2004
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400457
Subject(s) - chemistry , steric effects , pyran , intramolecular force , stereoselectivity , cyclohexane , diol , stereochemistry , bromide , ring (chemistry) , anomer , medicinal chemistry , organic chemistry , catalysis
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 Königs−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 BF 3 ‐mediated reduction with triethylsilane, the 1 H NMR spectroscopic data of the respective products 14 , 15 , 18 and 28 being instrumental in assigning their linkage geometries. Slightly basic conditions ( n Bu 4 NOAc 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)