MOLECULAR RECOGNITION OF PYRANOSIDES BY A FAMILY OF TRIMERIC, 1,1'-BINAPHTHALENE-DERIVED CYCLOPHANE RECEPTORS

The synthesis and carbohydrale-recognition properties of a new family of optically active cyclophane receptors, 1-3, in which three 1,1'-bin aphthalene-2,2'-diol spacers are interconnected by three bula-1,3-diyn ediyl linkers, are described. The macrocycles all contain highly preor ganized cavities lined with six convergent OH groups for H-bonding and complementary in size and shape to monosaccharides. Compounds 1-3 dif fer by the functionality attached to the major groove of the 1,1'-bina phthalene-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'-positio ns. The preparation of the more planar, D-3-symmetrical receptors (R,R ,R)-1(Schemes I and 2), (S,S;S)-1 (Scheme 4), (S,S,S)-2 (Scheme 5), an d (S,S,S)-3 (Scheme 8) involved as key step the Glaser-Hay cyclotrimer ization of the corresponding OH-protected 3,3'-dielhynyl-1,1'-binaphth alene-2,2'-diol precursors, which yielded tetrameric and pentameric ma crocycles in addition to the desired trimeric compounds. The synthesis of the less planar, C-2-symmetrical receptors (R,R,S)-2 (Scheme 6) an d (S,S,R)-3 (Scheme 9) proceeded via two Glaser-Hay coupling steps. Fi rst, two monomeric precursors of identical configuration were oxidativ ely 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 Stifle (Scheme I) 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 oct yl 1-O-pyranosides in CDCl3 (300 K) with moderate stability (Delta G d egrees ca. -3 kcal mol(-1)) as well as moderate diastereo(Delta(Delta G degrees) up to 0.7 kcal mol(-1)) and enantioselectivity (Delta(Delta G degrees) = 0.4 kcal mol(-1)) ( Table I). Stoichiometric 1 : 1 compl exation by (S,S,S)-2 and (S,S,S)3 could not be investigated by H-1-NMR binding titrations, due to very strong signal broadening. This broade ning of the H-1-NMR resonances is presumably indicative of higher-orde r associations, in which the planar macrocycles sandwich the carbohydr ate guests. The less planar Ct-symmetrical receptor (S,S,R)-3 formed s table 1: 1 complexes with binding free enthalpies of up to Delta G deg rees = - 5.0 kcal mol(-1) (Table 2). With diastereoselectivities up to Delta(Delta G degrees)=1.3 kcal mol(-1) and enantioselectivities of D elta(Delta G degrees)= 0.9 kcal mol(-1), (S,S,R)-3 is among the most s elective artificial carbohydrate receptors known.