目的 设计合成双荧光素修饰的6A, 6D-双脱氧-α-环糊精。方法 从α-环糊精出发,经过苄基化保护得到过苄基化-α-环糊精(1),特定温度下利用DIBAL-H对过苄基化-α-环糊精进行选择性脱保护,得到中间体2,中间体2经磺酰化、叠氮化后将6A, 6D位点上伯醇转化为叠氮,再经氢化铝锂还原为伯胺。再在钯碳/氢气条件脱除苄基保护,获得6A,6D-双脱氧-6A,6D-二氨基-α-环糊精(6)。碱性条件下,中间体6与两倍当量的异硫氰基荧光素发生亲核加成反应,得到6A, 6D-双脱氧-6A, 6D-双荧光素-α-环糊精(7)。结果 6个中间体和1个目标产物的结构经过核磁共振氢谱和质谱确证。结论 成功设计合成双荧光素修饰的6A,6D-双脱氧-α-环糊精(7),并且获得新的环糊精衍生物6A,6D-氧-对甲苯磺酰基-2A-F,3A-F,6B,6C,6E,6F-十六氧苄基-α-环糊精(3)。
Abstract
OBJECTIVE Design and synthesis of 6A, 6D-dideoxy-6A, 6D-bifluorescein-α-cyclodextrin. METHODS Perbenzylated-α-cyclodextrin (1) is obtained through benzylation protection of α-cyclodextrin, and the perbenzylated-α-cyclodextrin (1) is then selectively de-O-alkylated by DIBAL-H at a specific temperature, so that the intermediate 2 is obtained. After being sulfonylated, azided, primary alcohol of intermediate 2 on 6A, 6D site is converted into azide group, and then reduced to primary amine through lithium aluminum hydride. Under the condition of palladium carbon/hydrogen, the benzyl protection was removed to afford 6A, 6D-dideoxy-6A,6D-diamino-α-cyclodextrin (6). Under alkaline condition, intermediate 6 undergoes a nucleophilic addition reaction with twice the equivalent amount of isothiocyanofluorescein to give 6A, 6D-dideoxy-6A, 6D-difluorescein-α-cyclodextrin (7). RESULTS The structures of 6 intermediates and 1 target product were confirmed by 1H-NMR and MS. CONCLUSION Successfully designed and synthesized double fluorescein-modified 6A, 6D-deoxy-α-cyclodextrin (7), and obtained a new intermediate compound 6A, 6D-oxy-p-toluenesulfonyl-2A-F, 3A-F, 6B, 6C, 6E, 6F-hexadecyloxybenzyl-α-cyclodextrin (3).
关键词
α-环糊精 /
荧光素 /
荧光素修饰 /
荧光探针
{{custom_keyword}} /
Key words
α-cyclodextrin /
fluorescein /
fluorescence modification /
fluorescent probe
{{custom_keyword}} /
中图分类号：
R944
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] TIAN B, HUA S, TIAN Y, et al. Cyclodextrin-based adsorbents for the removal of pollutants from wastewater: A review[J]. Environ Sci Pollut Res, 2021, 28 (2):1317-1340.
[2] TANG W, ZOU C, DA C, et al. A review on the recent development of cyclodextrin-based materials used in oilfield applications[J]. Carbohydr Polym, 2020, 240: 116321.
[3] HE Y Q, C L, HE R L, ZHONG K L, et al. Research progress of fluorescence probes constructed by cyclodextrin derivatives and inclusion complexes[J]. Chin J Organ Chem, 2022, 42(3): 785-795.
[4] HANESSIAN S, BENALIL A, LAFERRIÈRE C A. The synthesis of functionalized cyclodextrins as scaffolds and templates for molecular diversity, catalysis, and inclusion phenomena[J]. J Org Chem, 1995, 60(15):4786-4797.
[5] FREDY J W, SCELLE J, RAMNICEANU G, et al. Mechanostereoselective one-pot synthesis of functionalized head-to-head cyclodextrin [3]rotaxanes and their application as magnetic resonance imaging contrast agents[J]. Organ Lett, 2017, 19 (5):1136-1139.
[6] KOTKOVA Z, KOTEK J, JIRAK D, et al. Cyclodextrin-based bimodal fluorescence/mri contrast agents: An efficient approach to cellular imaging[J]. Chemistry, 2010, 16 (33):10094-10102.
[7] LECOURT T, HERAULT A, PEARCE A J, et al. Triisobutylaluminium and diisobutylaluminium hydride as molecular scalpels: The regioselective stripping of perbenzylated sugars and cyclodextrins[J]. Chemistry, 2004, 10 (12):2960-2971.
[8] JESSICA W, M G E, AURORA R R, et al. Chemistry of mri contrast agents: Current challenges and new frontiers [J]. Chem Rev, 2019, 119 (2):957-1057.
[9] CAO L, QU Y, HU C, et al. A universal and versatile approach for surface biofunctionalization: Layer-by-layer assembly meets host-guest chemistry[J]. Adv Mater, 2016, 3 (18):1600600.
[10] YU G, ZHAO X, ZHOU J, et al. Supramolecular polymer-based nanomedicine: High therapeutic performance and negligible long-term immunotoxicity[J]. J Am Chem Soc 2018, 140 (25):8005-8019.
[11] FREDY D J W, SCELLE J, GUENET D A, et al. Cyclodextrin polyrotaxanes as a highly modular platform for the development of imaging agents[J]. Chemistry, 2014, 20 (35):10915-10920.
[12] PEARCE A J, SINA P. Diisobutylaluminum-promoted regioselective de-o-benzylation of perbenzylated cyclodextrins: A powerful new strategy for the preparation of selectively modified cyclodextrins[J]. Angew Chem Int Ed, 2000, 39 (20):3610-3612.
[13] DEUNF E, ZABOROVA E, GUIEU S, et al. Synthesis and electrochemical study of an original copper(ii)-capped salen-cyclodextrin complex[J]. Eur J Inorg Chem, 2010, 2010 (29):4720-4727.
[14] YIN J J, SHARMA S, SHUMYAK S P, et al. Synthesis and biological evaluation of novel folic acid receptor-targeted, beta-cyclodextrin-based drug complexes for cancer treatment[J]. PLoS One, 2013, 8 (5):e62289.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然基金仪器专项资助(61827808)
{{custom_fund}}
PDF(1287 KB)
