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Molecular Recognition of Pyranosides by a Family of Trimeric, 1,1′‐Binaphthalene‐Derived Cyclophane Receptors
Author(s) -
Bähr Anja,
Droz Anne Sophie,
Püntener Martin,
Neidlein Ulf,
Anderson Sally,
Seiler Paul,
Diederich François
Publication year - 1998
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19981111)81:11<1931::aid-hlca1931>3.0.co;2-5
Subject(s) - chemistry , cyclophane , monomer , stereochemistry , diol , planar chirality , molecular recognition , receptor , crystallography , molecule , crystal structure , polymer chemistry , organic chemistry , enantioselective synthesis , biochemistry , catalysis , polymer
The synthesis and carbohydrate‐recognition properties of a new family of optically active cyclophane receptors, 1 – 3 , in which three 1,1′‐binaphthalene‐2,2′‐diol spacers are interconnected by three buta‐1,3‐diynediyl linkers, are described. The macrocycles all contain highly preorganized cavities lined with six convergent OH groups for H‐bonding and complementary in size and shape to monosaccharides. Compounds 1 – 3 differ by the functionality attached to the major groove of the 1,1′‐binaphthalene‐2,2′‐diol spacers. The major grooves of the spacers in 2 are unsubstituted, whereas those in 1 bear benzyloxy (BnO) groups in the 7,7′‐positions and those in 3 2‐phenylethyl groups in the 6,6′‐positions. The preparation of the more planar, D 3 ‐symmetrical receptors ( R , R , R )‐ 1 ( Schemes 1 and 2 ), ( S , S , S )‐ 1 ( Scheme 4 ), ( S , S , S )‐ 2 ( Scheme 5 ), and ( S , S , S )‐ 3 ( Scheme 8 ) involved as key step the Glaser‐Hay cyclotrimerization of the corresponding OH‐protected 3,3′‐diethynyl‐1,1′‐binaphthalene‐2,2′‐diol precursors, which yielded tetrameric and pentameric macrocycles in addition to the desired trimeric compounds. The synthesis of the less planar, C 2 ‐symmetrical receptors ( R , R , S )‐ 2 ( Scheme 6 ) and ( S , S , R )‐ 3 ( Scheme 9 ) proceeded via two Glaser‐Hay coupling steps. First, two monomeric precursors of identical configuration were oxidatively coupled to give a dimeric intermediate which was then subjected to macrocyclization with a third monomeric 1,1′‐binaphthalene precursor of opposite configuration. The 3,3′‐dialkynylation of the OH‐protected 1,1′‐binaphthalene‐2,2′‐diol precursors for the macrocyclizations was either performed by Stille ( Scheme 1 ) or by Sonogashira ( Schemes 4 , 5 , and 8 ) cross‐coupling reactions. The flat D 3 ‐symmetrical receptors ( R , R , R )‐ 1 and ( S , S , S )‐ 1 formed 1 : 1 cavity inclusion complexes with octyl 1‐ O ‐pyranosides in CDCl 3 (300 K) with moderate stability ( Δ G 0 ca. −3 kcal mol −1 ) as well as moderate diastereo‐ ( Δ ( Δ G 0 ) up to 0.7 kcal mol −1 ) and enantioselectivity ( Δ ( Δ G 0 )=0.4 kcal mol −1 ) ( Table 1 ). Stoichiometric 1 : 1 complexation by ( S , S , S )‐ 2 and ( S , S , S )‐ 3 could not be investigated by 1 H‐NMR binding titrations, due to very strong signal broadening. This broadening of the 1 H‐NMR resonances is presumably indicative of higher‐order associations, in which the planar macrocycles sandwich the carbohydrate guests. The less planar C 2 ‐symmetrical receptor ( S , S , R )‐ 3 formed stable 1 : 1 complexes with binding free enthalpies of up to Δ G 0 =−5.0 kcal mol −1 ( Table 2 ). With diastereoselectivities up to Δ ( Δ G 0 )=1.3 kcal mol −1 and enantioselectivities of Δ ( Δ G 0 )=0.9 kcal mol −1 , ( S , S , R )‐ 3 is among the most selective artificial carbohydrate receptors known.