What molecule am I?
Fondaparinux is a low–molar mass pentasaccharide derivative used to prevent and treat deep-vein thrombosis. It was first reported in 1987, when Maurice Petitou at Institut Choay (Paris) and collaborators there and at Laboratoire de Biochimie Structurale (Orléans, France) and Istituto di Chimica e Biochimica “G. Ronzoni” (Milan, Italy) described the synthesis of a methyl α-pentoside with high affinity for antithrombin III1 (AT), a glycoprotein that inactivates coagulation enzymes.
The molecule exists in two forms: a neutral polyacid, called heparin pentasaccharide2 that includes sulfonic, oxysulfonic, and carboxylic acids; and the decasodium salt of those acids. The salt, fondaparinux, is the preferred form because of its superior bioavailability.
In 2005, an article by Jeanine M. Walenga and coauthors at Loyola University Medical Center (Maywood, IL) described fondaparinux as the first of a class of antithrombotic agents distinct from heparin3 and its low–molar mass derivatives. They noted that the synthetic compound mimics the site of heparin that binds to AT but exhibits only factor Xa inhibitor activity, which maximizes the inhibition of thrombin generation.
The following year, Kenneth A. Bauer and coauthors (including Petitou) at several institutions in the United States, France, and the Netherlands reviewed the findings on fondaparinux, stating that the pentasaccharide’s complete bioavailability and rapid absorption demonstrate its superiority over heparin and its derivatives. They also pointed out that fondaparinux has a terminal half-life of 13–21 h, which allows once-daily dosing.
Finally, in 2019, Yili Ding* and Bingyun Wang at Fushan University (Guangdong, China) and Chamakura V. N. S. Vara Prasad* at Das Pharma (Kakinada, India) reviewed improved syntheses of fondaparinux, which is characteristically difficult and expensive to make. Most of the improvements (all of which had some drawbacks) involved strategies for connecting the five rings of the molecule and minimizing the number of functional group protection and deprotection steps. The authors suggested a potentially practical method for synthesizing the compound.
1. CAS Reg. No. 9000-94-6.
2. CAS Reg. No. 104993-28-4.
3. CAS Reg. No. 9005-49-6.
Fondaparinux hazard information*
| Hazard class** | GHS code and hazard statement | |
|---|---|---|
| Acute toxicity, oral, category 4 | H302—Harmful if swallowed |  |
| Serious eye damage/eye irritation, category 2A | H319—Causes serious eye irritation | |
| Acute toxicity, inhalation, category 4 | H332—Harmful if inhaled | |
| Specific target organ toxicity, repeated exposure, category 1 | H372—Causes damage to organs*** through prolonged or repeated exposure |  |
*Compilation of multiple safety data sheets.
**Globally Harmonized System (GHS) of Classification and Labeling of Chemicals. Explanation of pictograms.
***Organs not specified.
Paltusotine1 is a small-molecule drug under development as a treatment for acromegaly, an endocrine disease caused by the formation of excess human growth hormone. It is an orally available, nonpeptide, selective somatostatin receptor type 2 (SST2) agonist that is also effective against carcinoid syndrome associated with neuroendocrine tumors.
Paltusotine was first described in world patent WO2018013676 to Jian Zhao and co-inventors at Crinetics Pharmaceuticals (San Diego). In 2022, Zhao, Stephen F. Betz, and co-workers at Crinetics reported details of the synthesis, mode of action, pharmokinetic properties, and efficacy of paltusotine. The drug is in Phase 3 trials in acromegaly patients and Phase 2 trials in neuroendocrine tumor patients.
1. CAS Reg. No. 2172870-89-0.
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Fondaparinux
fast facts
| CAS Reg. No. | 114870-03-0 |
| SciFindern name | Fondaparinuxa |
| Empirical formula | C31H43N3Na10O49S8 |
| Molar mass | 1728.03 g/mol |
| Appearance | White powder |
| Melting point | >290 °C (dec.) |
| Water solubility | 20 g/L |
a. Full name: α-D-Glucopyranoside, methyl O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl-(1→4)-O-β-D-glucopyranuronosyl-(1→4)-O-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl-(1→4)-O-2-O-sulfo-α-L-idopyranuronosyl-(1→4)-2-deoxy-2-(sulfoamino)-, 6-(hydrogen sulfate), sodium salt.
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