An efficient synthesis of novel sucrose-containing dilactams

Abstract An efficient and convenient approach to sucrose-containing dilactams has been developed. The method, based on reaction of regioisomeric 6,6′-di-O-[(aminomethyl)-phenyl]-1′,2,3,3′,4,4′-hexa-O-methylsucrose with isophtaloyl or 2,6-pyridinedicarbonyl dichlorides, provided the 1:1-macrocycles in good yields. Graphical Abstract .


Introduction
Macrocyclic compounds are important in supramolecular chemistry [1]. Especially interesting are chiral receptors capable of enantioselective complexation of a variety of important chiral guests. Carbohydrates, inexpensive, renewable raw materials available optically pure, are particularly useful in planning and executing the synthesis of such chiral hosts. The different configurations and conformations of carbohydrates can be incorporated in the target macrocycle, which makes these compounds convenient chiral synthetic analogs of poly(ethylene glycol) (PEG) reagents [2]. Chiral crown and aza-crown ethers with carbohydrate scaffolds have been extensively used as chiral catalysts in asymmetric synthesis (asymmetric epoxidation of chalcones [3][4][5], Michael addition [3,4,6,7], and Darzens reactions [3-5, 7, 8]). Carbohydrate-containing macrocycles have also been investigated as fluorescent molecular sensors for cations [9,10] and anions [11].
Isophthalic and pyridine-2,6-diamides, because of their proton-donor properties, are convenient scaffolds used as building blocks in the synthesis of macrocyclic receptors designed for complexation of anions [16], ion pairs [17], zwitterions [18], and amino acid derivatives [19]. The anion-complexing properties of such diamides have been exploited in templated syntheses of catenane [20] and rotaxane [21] systems. Macrocycles incorporating the pyridine-2,6-diamide functionality are known as molecular turnstiles [22]. Combination of the sucrose scaffold with isophthalic or pyridine-2,6-diamide units may be useful means of synthesis of a new type of chiral receptor with interesting properties.
A crucial aspect of the synthesis of this type of receptor is the relative orientation of the two amino groups in the energetically accessible conformations of the substrates. The amino groups in the p-substituted derivative 2c are rather distant from each other (compared with the o and m analogs 2a and 2b). Thus, the intermediate formed in reaction of the acid dichloride (5 or 6) with the first amino group will react preferentially with a second molecule of 2c (to form the dimer) rather than undergo the intramolecular process leading to 3c or 4c [23].

Results and Discussion
In this paper we report the synthesis of new sucrose macrocyclic derivatives which are twice homologated compared with compounds 3a-3c and 4a-4c. Arylmethaneamines 9a-9c (the homologated analogs of anilines 2a-2c) were used as starting materials for the preparation of conformationally less demanding structures.
In summary, we have developed a simple, rapid, and efficient procedure for preparation of sucrose-based promising optically active receptors. Because of the conformational mobility (less rigid structure) of the diamine 9c, which differ from 2c (which furnishes both the monomers and the dimers in the reaction with dichlorides 5 or 6; Scheme 1) only in the length of the chain, we were able to suppress formation of the dimer and obtain monomeric macrocycles in good yield. This strategy was applicable to the synthesis of sucrose-derived macrocycles containing isophthalic and pyridine-2,6-diamide groups.

Experimental
All reported NMR spectra were recorded with a Varian Vnmrs-600 MHz spectrometer (at 600 and 150 MHz for 1 H and 13 C NMR spectra, respectively); solutions were prepared in CDCl 3 with TMS as the internal standard. Most of the resonances were assigned by COSY ( 1 H-1 H) and gradient selected HSQC and HMBC correlations. IR spectra (CHCl 3 , film) were recorded on a Perkin Elmer FT-IR Spectrum 2000. Mass spectra were recorded with an ESI/MS Mariner (PerSeptive Biosystem) mass spectrometer. Elemental analysis was performed with a Perkin-Elmer 2400 CHN analyzer; results agreed satisfactorily with calculated values. Optical rotation was measured with a Jasco DIP-360 digital polarimeter; solutions were prepared in CH 2 Cl 2 (c = 1). Flash chromatography was performed on silica gel (Merck, 230-400 mesh). The organic phases were dried over anhydrous magnesium sulfate.
General procedure for syntheses of macrocyclic diamides 10a-10c and 11a-11c This reaction was conducted under an argon atmosphere: 35 mg isophthaloyl or 2,6-pyridinedicarbonyl dichloride (5 or 6, 0.17 mmol) was dissolved in 20 cm 3 dry CH 2 Cl 2 and added dropwise to a stirred solution of 108 mg diamine 9a-9c (0.17 mmol) in 40 cm 3 dry CH 2 Cl 2 containing 71 mm 3 Et 3 N (0.51 mmol), and the mixture was stirred for 1 h at room temperature. The resulting solution was concentrated in vacuum and the residue was dissolved in 40 cm 3 ethyl acetate and 20 cm 3 water. Saturated K 2 CO 3 solution (10 cm 3 ) was added, the layers were separated, and the aqueous layer was extracted with ethyl acetate (3 9 30 cm 3 ). The combined organic extracts were washed with 20 cm 3 water and 10 cm 3 brine, dried, concentrated, and the products were isolated by flash chromatography (hexane-ethyl acetate, 50:50 to 25:75).