Synthesis and Crystal Structure of Anhydrous Analog of 1, 25‐Dihydroxyvitamin D3. Issue 11 (14th August 2013)

• Record Type: Journal Article
• Authors: Pietraszek, Anita; Malińska, Maura; Chodyński, Michał; Martynow, Jacek; Krupa, Małgorzata; Maruszak, Wioleta; Woźniak, Krzysztof; Kutner, Andrzej
• Is Part Of: Journal of pharmaceutical sciences. Volume 102:Issue 11(2013:Nov.)
• Page Start: 3925
• Page End: 3931
• Publication Date: 2013-08-14
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23701
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>As predicted by single crystal X‐ray crystallography, and contrary to the reported suggestions, the anhydrous form of calcipotriol, a therapeutically important vitamin D analog, was found stable enough to be used as an active pharmaceutical ingredient. The crystal and molecular structure of calcipotriol anhydrate was solved and refined using single crystal X‐ray diffraction. The analog was obtained by a novel convergent synthesis from the vitamin D C‐22 sulfone, as an advanced intermediate and a side‐chain fragment. The homo‐chiral side‐chain aldehyde was obtained from cyclopropanecarboxyaldehyde by the chromatographic separation of the intermediate diastereomeric salts with (<italic>S</italic>)‐naproxen. Calcipotriol anhydrate showed a single peak in differential scanning calorimetry and the absence of a peak from a water molecule, typical for the monohydrate. Calcipotriol anhydrate, as the only 1, 25‐dihydroxylated analog of vitamin D<sub>3</sub>, exists as a mixture of both α‐ and β‐forms of the A‐ring, present in the asymmetric part of the unit cell of the crystal lattice. The intermolecular hydrogen bonding between both conformers in the crystal lattice indicated that the stability of calcipotriol anhydrate might be at least the same as for the known monohydrate. The usefulness of calcipotriol anhydrate as an active pharmaceutical ingredient was confirmed by the stability study in the standard conditions used for the storage of vitamin D analogs. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3925–3931, 2013</p> </abstract>