Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite

Abstract

SummaryWe achieved the synthesis of important medronic acid monoalkyl esters via the dealkylation of mixed trimethyl monoalkyl esters of medronic acid. Two methods were developed for the purification of medronic acid monoesters: 1) small scale (10–20 mg) purification by using hydroxyapatite and 2) large scale (tested up to 140 mg) purification by high-performance countercurrent chromatography (HPCCC).

Synthesis and Theoretical Studies of Aromatic Azaborines

“…All the NMR samples were dissolved in CDCl3 and measured by Bruker Avan III HD NMR spectrometer equipped with CryoProbe. 1 H and 13 C NMR spectra were re In our unpublished studies related to boronate amino acids, we have encountered unexpected reactions caused by the empty p-orbital of boron. One of these was the formation of azaborines despite attempts to protect boronic acid as an ester during Horner-Wadsworth-Emmons reaction.…”

“…All the NMR samples were dissolved in CDCl 3 and measured by Bruker Avance III HD NMR spectrometer equipped with CryoProbe. 1 H and 13 C NMR spectra were recorded on a 600 MHz spectrometer operating at 600.2 and 150.9 MHz, respectively. Tetramehylsilane (TMS) was used as reference in NMR measurements.…”

“…We have earlier successfully used HPCCC for purification of bisphosphonate (medronate) monoesters [13] and biologically important adenosine triphosphate (ATP) analogues: ApppI [14] and ApppD [15]. Like in this reported research, those compounds were hard or even impossible to purify by conventional methods such as (flash) silica column chromatography or preparative TLC, besides HPCCC also offers a much higher capacity than HPLC and in our opinion, is better than HPLC in a number of other ways, as we have shortly discussed elsewhere.…”

“…In both 1 H and 13 C NMR spectra, all the compounds showed peaks for a distinct structure after long exposure in high vacuum, exposure to heating in NaOH solution or after exposure to different solvent systems after purification by High Performance Counter Current Chromatography (HPCCC). Major differences were found in the region of benzylic methylene protons that showed an AX doublet and in the region of methyl ester group.…”