Note Cite This: J. Org. Chem. 2018, 83, 5766−5770
pubs.acs.org/joc
Nonplanar Macrocycle Consisting of Four Pyridine and Phenol Units Connected with Acetylene Bonds Displaying Preferential Binding to Maltoside over Monosaccharides Yuki Ohishi, Naoto Yamamoto, Hajime Abe,‡ and Masahiko Inouye* Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan S Supporting Information *
ABSTRACT: A nonplanar macrocycle consisting of four pyridine−acetylene−phenol units was developed as a host for saccharide guest molecules. The macrocycle was found to strongly associate with a lipophilic maltose derivative, with an association constant of 107 M−1, over monosaccharide derivatives, for which much smaller association constants were determined, ranging from 103 M−1 to 104 M−1. The macrocycle was found to adopt a boat-like conformation, encapsulating β-D-maltoside in a twisted manner through approximately seven intermolecular hydrogen bonds.
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proposed to adopt a boat- and/or chair-shaped conformation.10 Therefore, host 2 was also expected to form three-dimensional complexes with saccharides. Indeed, Macro Model-based Monte Carlo simulations proposed that 2 adopts a boat-like structure, encapsulating β-D-maltose through seven intermolecular hydrogen bonds in a twisted manner (Figure 1D).8 Scheme 1 shows the synthetic procedure for macrocycle 2. The trimer building block 3 and 2,6-diiodo-4-(octyloxy)pyridine (4) were prepared according to literature methods.2a,11 A Sonogashira reaction using 3 and an excess amount of 4 yielded the pentamer precursor 5. Precursors 3 and 5 were reacted together under dilute conditions to give MOMprotected macrocycle 6 in an acceptable yield. Finally, the MOM groups of 6 were removed using trifluoroacetic acid (TFA) to produce target host 2. The self-aggregation of 2 was investigated by 1H NMR measurements in CDCl3 (Figure S1). The aromatic proton signals of 2 had a very simple pattern at lower concentrations ([2] < 1.0 × 10−3 M), whereas complicated signals appeared at a higher concentration range ([2] ≥ 1.0 × 10−3 M), independently of the NMR time scale. The complicated signals were found to disappear upon heating 2 or after the addition of MeOH, suggesting that the signals might be due to a hydrogenbonded, self-aggregated form of 2 (Figure S2B,C). On the basis of these NMR experiments, the self-aggregation of 2 was determined not to interfere with the saccharide interaction at a concentration of
