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Optimized synthesis of a per-O-methylated β-cyclodextrin dimer linked at the secondary face by a pyridine ligand

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Abstract

In a previous study, we reported a 1:1 complex (hemoCD) of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphinatoiron(II) (Fe(II)TPPS) with per-O-methylated β-cyclodextrin (CD) dimer having a pyridine (Py) linker, which was able to bind O2 and CO reversibly in aqueous solution. Among the CD dimers synthesized by us, the CD dimer (Py3OCD) that was linked via ether bonds at 3,3′-positions formed the best inclusion complex with Fe(II)TPPS and was utilized as an artificial O2 carrier and an antidote for cyanide anion poisoning. For practical applications, considerable amounts of Py3OCD need to be synthesized. However, the experimental conditions for the synthesis of Py3OCD have not been optimized as yet and an unidentified byproduct is sometimes obtained in the dimerization step. In this study, we identified the byproduct as the per-O-methylated CD dimer linked at the 6,6′-positions of two CDs. It was found that the undesired 6,6′-dimer was formed when the reaction temperature in the dimerization reaction was over 80 °C. This finding led us to effectively synthesize a large amount of Py3OCD in good yield, which is helpful for the practical use of hemoCD as an artificial O2 carrier or an antidote for cyanide anion.

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Acknowledgements

This work was financially supported by MEXT/JSPS KAKENHI (Grant Nos. 15H02569, 16K13092, 17H02208), the MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2015–2019), the Naito Foundation, Takeda Science Foundation, Suntory Foundation for Life Sciences, and JGC-S Scholarship Foundation.

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  1. Department of Molecular Chemistry and Biochemistry, Doshisha University, Kyotanabe, Kyoto, 610-0321, Japan

    Qiyue Mao & Hiroaki Kitagishi

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  1. Qiyue Mao
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  2. Hiroaki Kitagishi
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Correspondence to Hiroaki Kitagishi.

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Mao, Q., Kitagishi, H. Optimized synthesis of a per-O-methylated β-cyclodextrin dimer linked at the secondary face by a pyridine ligand. J Incl Phenom Macrocycl Chem 93, 67–76 (2019). https://doi.org/10.1007/s10847-018-0839-4

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  • DOI: https://doi.org/10.1007/s10847-018-0839-4

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