Strong binding and fluorescence sensing of bisphosphonates by guanidinium-modified calix[5]arene

• Jie Gao,
• Zhe Zheng,
• Lin Shi,
• Si-Qi Wu,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2018, 14, 1840–1845, doi:10.3762/bjoc.14.157

• 1:1 competitive binding model, giving the Ka values as listed in Table 1. Ibandronate, alendronate and neridronate gave an around 40–100 times weaker binding than etidronate, which is probably due to the aminoalkyl-substituents present in the former compounds. However, pamidronate having an

• aminoethyl substituent shows comparable binding to etidronate. At present, the reason for this behavior remains unclear. Overall, the strong binding of 9 BPs with GC5A with association constants in the μM to nM range is suitable for the following sensing study. By executing IDA based on the GC5A·Fl reporter

• pair, we realized the fluorescence “switch-on” sensing of BPs. We herein selected clodronate, zoledronate and etidronate to further investigate their quantitative detection. As shown in Figure 2a, increasing the concentrations of BPs resulted in a practically linear fluorescence increase. The limit of

Two strategies for the synthesis of the biologically important ATP analogue ApppI, at a multi-milligram scale

• Janne Weisell,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2015, 11, 2189–2193, doi:10.3762/bjoc.11.237

• , with osteoporosis probably being the most well-known indication [1][2]. BPs can be separated into two groups: non-nitrogen containing BPs (non-N-BPs) such as etidronate and clodronate, and nitrogen containing BPs (N-BPs) like pamidronate, alendronate and risedronate (Figure 1) [2]. BPs from these two

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

• Petri A. Turhanen,
• Janne Weisell and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2012, 8, 2019–2024, doi:10.3762/bjoc.8.228

• Petri A. Turhanen Janne Weisell Jouko J. Vepsalainen University of Eastern Finland, School of Pharmacy, Biocenter Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland 10.3762/bjoc.8.228 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. Keywords: alkyl carbonate; bisphosphonate; etidronate; ester

Unexpected degradation of the bisphosphonate P-C-P bridge under mild conditions

• Petri A. Turhanen and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2008, 4, No. 7, doi:10.1186/1860-5397-4-7

• Petri A. Turhanen Jouko J. Vepsalainen University of Kuopio, Department of Biosciences, Laboratory of Chemistry, PO Box 1627, FIN-70211, Kuopio, Finland 10.1186/1860-5397-4-7 Abstract Unexpected degradation of the P-C-P bridge from novel bisphosphonate derivative 1a and known etidronate trimethyl

• BPs in detail. Etidronate, (1-hydroxyethylidene)-1,1-bisphosphonic acid (HEBPA) disodium salt, is one of the earliest synthesized and is the most extensively investigated BP compound, still being in clinical use today (Figure 1) [1][2][3][4][5][6][15]. Our group has designed, synthesized and studied

• in vitro several different etidronate and alendronate derivatives to act as biodegradable prodrugs of these drugs [16][17][18][19][20][21][22][23]. During our ongoing study to prepare new, possibly bioreversible BP derivatives, we observed unexpected degradation of the P-C-P bridge under mild

Synthesis of novel (1-alkanoyloxy- 4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives

• Petri A. Turhanen and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2006, 2, No. 2, doi:10.1186/1860-5397-2-2

• acid groups with a biodegradable ester or amide functionality. Our group has designed, synthesized and studied in vitro several different clodronate (R1 = R2 = Cl, Figure 1) and etidronate (R1 = CH3 R2 = OH, Figure 1) ester and amide derivatives to act as biodegradable prodrugs. [15][16][17][18][19] We

• have also recently described the method for the preparation of (1-alkoxycarbonyloxyethylidene)-1,1-bisphosphonic acid derivatives [20] and novel fatty acid derivatives of etidronate [21] which may represent prodrugs of etidronate. In the case of etidronic acid, we have shown that simple phosphonate