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通过一条不寻常的路线制备混合三烷基碳酸二膦酸乙酯衍生物。

Preparation of mixed trialkyl alkylcarbonate derivatives of etidronic acid via an unusual route.

机构信息

University of Eastern Finland, School of Pharmacy, Biocenter Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland.

出版信息

Beilstein J Org Chem. 2012;8:2019-24. doi: 10.3762/bjoc.8.228. Epub 2012 Nov 20.

DOI:10.3762/bjoc.8.228
PMID:23209537
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3511037/
Abstract

A method to prepare four (3a-d) trialkyl alkylcarbonate esters of etidronate from P,P'-dimethyl etidronate and alkyl chloroformate was developed by utilizing unexpected demethylation and decarboxylation reactions. The reaction with the sterically more hindered isobutyl chloroformate at a lower temperature (90 °C) produced the P,P'-diester (2) as a stable intermediate product. A possible reaction mechanism is discussed to explain these methyl substitutions. These unusual reactions also clarify why it is difficult to prepare alkylcarbonate prodrugs from bisphosphonates. The compounds prepared were analysed by spectroscopic techniques.

摘要

从 P,P'-二甲叉乙基膦酸二乙酯和氯甲酸烷基酯出发，利用意外的脱甲基和脱羧反应，开发了一种制备 4 种（3a-d）依替膦酸三烷基酯的方法。在较低温度（90°C）下用位阻较大的异丁基氯甲酸酯进行反应，生成稳定的中间体 P,P'-二酯（2）。讨论了可能的反应机制来解释这些甲基取代。这些不寻常的反应也阐明了为什么很难从双膦酸盐制备碳酸酯前药。通过光谱技术分析了所制备的化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c2/3511037/ad9efec2d853/Beilstein_J_Org_Chem-08-2019-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c2/3511037/7957c5d1d3ae/Beilstein_J_Org_Chem-08-2019-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c2/3511037/9ac82ad46c3d/Beilstein_J_Org_Chem-08-2019-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c2/3511037/226984e73f54/Beilstein_J_Org_Chem-08-2019-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c2/3511037/ad9efec2d853/Beilstein_J_Org_Chem-08-2019-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c2/3511037/7957c5d1d3ae/Beilstein_J_Org_Chem-08-2019-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c2/3511037/9ac82ad46c3d/Beilstein_J_Org_Chem-08-2019-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c2/3511037/226984e73f54/Beilstein_J_Org_Chem-08-2019-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c2/3511037/ad9efec2d853/Beilstein_J_Org_Chem-08-2019-g005.jpg

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Synth Commun. 2004 Jan 1;34(2):331-344. doi: 10.1081/SCC-120027271. Epub 2011 Oct 18.
2
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Bone. 2011 Jul;49(1):20-33. doi: 10.1016/j.bone.2011.03.774. Epub 2011 Apr 9.
3
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Bioorg Med Chem. 2008 Apr 1;16(7):3652-60. doi: 10.1016/j.bmc.2008.02.016. Epub 2008 Feb 8.
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5
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6
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