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

Abstract A novel strategy for the synthesis of (1-alkanoyloxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives (1a-d) via (1-hydroxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives (2a-d), starting from alendronate has been developed with reasonable 51-77% overall yields. Intermediate products, (1-hydroxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives (2a-d), were prepared in water with reasonable to high yields (52-94%)

Synthesis and Theoretical Studies of Aromatic Azaborines

Organoboron compounds are well known for their use as synthetic building blocks in several significant reactions, e.g., palladium-catalyzed Suzuki-Miyaura cross-coupling. As an element, boron is fascinating; as part of a molecule it structurally resembles a three-valent atom, but if there is a lone pair of electrons nearby, the boron atom’s empty p-orbital may capture the lone pair and form a covalent bond. This is the main aspect that is challenging chemistry during the synthesis of boron containing molecules and may lead into unexpected reactions and products. To study this, we synthesized and studied novel aromatic azaborines for better understanding of their structures and reactions. Here, we report a one-pot method for the synthesis of substituted aromatic azaborines and computational studies of their structure to explain their observed chemical properties.Peer reviewe

3-(3-Bromophenyl)-7-acetoxycoumarin

In natural product synthesis, the procurement of easily accessible starting materials is crucial. Chromenones and their subclass, coumarins, are a wide family of small, oxygen-containing aromatic heterocycles. Phenylcoumarins offer a particularly excellent starting point for a diverse chemical space of natural products, and thus are excellent staring materials for more complex natural products. Herein, we report an efficient synthesis of an easily accessible 3-phenylcoumarin bearing two orthogonally substitutable groups, bromine, and an acetyl-protected phenylic hydroxyl group

6-Bromo-1-hydroxyhexane-1,1-bisphosphonic Acid Monosodium Salt

The synthesis of 6-bromo-1-hydroxyhexane-1,1-bisphosphonic acid monosodium salt has been described in detail and characterized by 1H, 13C, 31P NMR spectroscopy and high-resolution MS methods. Bisphosphonates are highly important compounds having a lot of medicinal and non-medicinal applications

3-(3-Bromophenyl)-7-acetoxycoumarin

In natural product synthesis, the procurement of easily accessible starting materials is crucial. Chromenones and their subclass, coumarins, are a wide family of small, oxygen-containing aromatic heterocycles. Phenylcoumarins offer a particularly excellent starting point for a diverse chemical space of natural products, and thus are excellent staring materials for more complex natural products. Herein, we report an efficient synthesis of an easily accessible 3-phenylcoumarin bearing two orthogonally substitutable groups, bromine, and an acetyl-protected phenylic hydroxyl group

Synthesis of a Biologically Important Adenosine Triphosphate Analogue, ApppD

The chemical synthesis of a adenosine triphosphate analogue, 1-adenosin-5′-yl 3-(3-methylbut-2-enyl) triphosphoric acid diester (ApppD), is described. ApppD is known to be an active metabolite of the mevalonate pathway in the human body like its structural isomer isopentenyl ester of ATP (ApppI). Very recently, ApppI has been found to possess novel function(s); now it will also be possible to examine the effects of ApppD more precisely because it can be synthesized in reasonable amounts. 1-Adenosin-5′-yl 3-(3-methylbut-2-enyl) diphosphoric acid diester (AppD; a adenosine diphosphate analogue) was also isolated from the synthesis mixture. Both ApppD and AppD were characterized by ¹H, ¹³C, ³¹P NMR and mass spectrometry methods

Synthesis of Triple-Bond-Containing 1‑Hydroxy-1,1-bisphosphonic Acid Derivatives To Be Used as Precursors in “Click” Chemistry: Two Examples

The synthesis of novel (ω-alkynyl-1-hydroxy-1,1-diyl)­bisphosphonic acid tetramethyl esters (<b>1a</b>–<b>c</b>), their <i>P</i>,<i>P</i>′-dimethyl esters (<b>2a</b>–<b>c</b>), and two trimethyl ester derivatives (<b>3a</b> and <b>3b</b>) is reported. The prepared compounds can be attached to many kinds of molecules containing azide (−N₃) functionalities using a “click” chemistry approach. As an example, bisphosphonate trimethyl ester <b>3a</b> and <i>P</i>,<i>P</i>′-dimethyl ester <b>2b</b> were attached to triethylene glycol to form triethylene glycol–bisphosphonate conjugates <b>4</b> and <b>5</b> as model compounds for further studies in, for example, nanoparticle targeting

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

Two strategies for the synthesis of the ATP (adenosine triphosphate) analogue ApppI [1-adenosin-5’-yl 3-(3-methylbut-3-enyl)triphosphoric acid diester] (1) are described. ApppI is an active metabolite of the mevalonate pathway and thus is of major biological significance. Chemically synthezised ApppI was purified by using triethylammonium bicarbonate as the counter ion in ion-pair chromatography and characterized by 1H, 13C, 31P NMR and MS spectroscopical methods

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

We 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)