Structure and absolute configuration of a monohydrate of calcipotriol, (1α,3β,5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1,3,24-triol

Larsen, S.; Hansen, E. T.; Hoffmeyer, L.; Rastrup-Andersen, Niels

doi:10.1107/s010827019201031x

Cited by 5 publications

(5 citation statements)

References 4 publications

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“…This is why some geometrical restrains were required during the refinement. The side‐chain in the monohydrate and anhydrate is not planar, opposite to the one in the calcitriol trihydrate . Additionally, the C16A atomic position is disordered in the D‐ring.…”

Section: Resultsmentioning

confidence: 95%

“…The crystal and molecular structure of the 1α‐hydroxylated vitamin D compound was first determined by Larsen et al from the Leo Pharmaceutical Products for calcipotriol monohydrate. However, the conformation of the A‐ring in this work was erroneously called the α‐form and remained uncorrected in the erratum of this paper by the same authors . The single crystal structure of the hormonal form of vitamin D 3 was solved for trihydrate of 1,25‐(OH) 2 D 3 .…”

Section: Introductionmentioning

confidence: 99%

“…According to the current experience in the field, oligohydrates of 1α‐hydroxylated analogs of vitamin D 3 [Fig. , calcitriol ( 1 ), tacalcitol, and calcipotriol ( 2 )] have long been considered more suitable for pharmaceutical use than the respective anhydrates. However, based on our long pharmaceutical experience with calcitriol ( 1 ) anhydrate, we hypothesized that calcipotriol ( 2 ) anhydrate should also be stable enough for pharmaceutical use.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Crystal Structure of Anhydrous Analog of 1,25-Dihydroxyvitamin D3

Pietraszek

Malińska

Chodyński

et al. 2013

Journal of Pharmaceutical Sciences

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Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis and Crystal Structure of Anhydrous Analog of 1,25-Dihydroxyvitamin D3

Pietraszek

Malińska

Chodyński

et al. 2013

Journal of Pharmaceutical Sciences

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“…All of them were analyzed to find packing similarity 30 and hydrogen bond motifs with the aid of the Mercury program. 31 CSD refcodes: EFEHII, EFEHOO, 32 GAJNOX, GAJNUD, 33 HIJFAH, 34 KAKTOH, 35 MIJXUA 21 NAJPOE, NAJPUK, 36 QURJUI, 37 SUJ-CUX, 15 TEZPIZ, TEZPOF, TEZQAS, 38 WACHIR, 39 WUTVUD, 40 and ZUNFUL 41 (Figure S1, Supporting Information). One of the mentioned analogues HIJFAH (crystal structure of hydrated 1,25D 3 ) was used in computational studies as a reference molecule.…”

Section: Methodsmentioning

confidence: 99%

Effect of Vitamin D Conformation on Interactions and Packing in the Crystal Lattice

Wanat

Malińska

Kutner

et al. 2018

Crystal Growth & Design

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The crystal and molecular structures of a series of structurally related analogues of 1,25-dihydroxyvitamin D2 and of the first analogue with all hydroxyl groups protected were established with single crystal X-ray structural analysis. With the use of the new structural data, we proposed that the A-ring conformation depends on hydrogen bonding of the hydroxyl groups of the A-ring. The A-ring of the 1α-hydroxylated vitamin D analogues exists in the solid state in a preferred chair β-conformation induced by direct hydrogen bonds between the 1-OH and 3-OH hydroxyl groups. In the same A-ring conformation, the vitamin D analogue interacts with the vitamin D receptor. Indirect hydrogen bonds between the A-ring hydroxyl groups, such as the ones through the water molecule, or hydrogen bonds between the A-ring hydroxyl groups and side-chain hydroxyl groups, induce the α-conformation. Theoretical calculations performed in vacuo showed that the β-form has a slightly lower energy than the α-form. Not only the hydroxyl groups but also the exocyclic methylene highly influences intermolecular interactions including the hydrogen bond pattern in the crystal lattices.

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“…The hydrogen bond in 25(OH)-VD 3 3) is head-to-tail type between the A ring and the chain terminal. There is a direct head-to-head type hydrogen bond between the 1OH-and 3OH-of the A rings in calcipotriol 4) and 1,25(OH) 2 -VD 3 . 5) In any case, no symmetrical dimer forms.…”

Section: Resultsmentioning

confidence: 99%

Dimer and Superstructure of the Active Form of a Vitamin D3. 1.ALPHA.,24(R)Dihydroxy-vitamin D3 Monohydrate, C27O3H44 H2O.

Koyano

Saitoh

Oshida

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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The structure of vitamin D was first analyzed on calciferol by heavy atom method in 1948.2) In 1977, 25-hydroxy-vitamin D 3 (25(OH)-VD 3 ) was solved by direct method precisely.3) Until the analysis of calcipotriol mono-hydrate in 1993, 4) the active form of vitamin D 3 in which the hydroxyl group is replaced at the 1a position by metabolism was not analyzed. Calcipotriol is a 1,24(R)(OH) 2 -type VD 3 , and has a rigid chain with a double bond and a terminal three-membered ring. In 1996, 1,25(OH) 2 -VD 3 was analyzed 5) as a trihydrate, of which two water molecules are disordered. The conformation of the A ring of both calcipotriol and 1,25(OH) 2 -VD 3 is b -form, that is, 3-OH is axial. 1a,24(R) (1,24(OH)2-VD 3 ; Fig. 1) has a linear chain like 25(OH)-VD 3 and 1,25(OH) 2 -VD 3 . It has the same activity as 1,25(OH)-VD 3 , and is especially applied to treat skin disease like psoriasis. It takes the crystal form of a superstructure, that is, its asymmetric unit consists of two subunits which are slightly different. The superstructure is difficult to solve, and only a few reports have been published on the subjects. In a centro-symmetrical crystal, it was solved using only reflections for the layers with subunits ("pseudo cell" in author's words) by direct method, but the accuracy is not good.6) In this case of an optically active molecule and a non centro-symmetrical crystal, reflections other than the layers of the subunits are not weak, nor absent. No direct method strategies were effective, 7,8) though they only suggested the existence of pseudo translation and pointed out the incompatibility of symmetry. Another method of integrated Patterson and direct methods 9,10) has been attempted here. ExperimentalCrystals of pharmaceutical from a methanol-water solution are too small for data collection; they were recrystallized from a dioxane-water (1 : 1) solution. Prismatic clear crystals 0.10ϫ0.10ϫ0.20 mm in size were obtained by slow evaporation. Crystal data from the different solutions are the same. , space group P2 1 2 1 2 1 . The asymmetric unit contains 4 molecules. Data were collected by Rigaku automated four-circle diffractometer RASA-5R, with w-2q scan mode, CuKa radiation and diffraction angle 2Ͻ2qϽ105°. Intensities decrease rapidly at higher diffraction angle. As the crystal is degradative, it was changed at every 5% decrease of monitoring 3 reflections. Three crystals were used, and three data sets were processed by TEXAN.11) Of the 6659 independent reflections, 4506F 2 O Ͼ0 were observed. For (0, k, 0) reflections, features other than systematic absence are, kϭ4n strong, kϭ2nϪ1 absent, kϭ4nϪ2 weak, indicative of a superstructure.Structure Determination and Refinement. Preparation As the search fragment model, the more rigid ring part of the A ring to the condensed C,D ring through a conjugated diene was selected from 25(OH)-VD 3 . The 1a oxygen atom was added and minimized by MMϩforce field.12) Super-sharpened Patterson function with coefficient (E 3 *F) 1/2 and the largest 200 E-values were calculat...

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Structure and absolute configuration of a monohydrate of calcipotriol, (1α,3β,5Z,7E,22E,24S)-24-cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1,3,24-triol

Cited by 5 publications

References 4 publications

Synthesis and Crystal Structure of Anhydrous Analog of 1,25-Dihydroxyvitamin D3

Synthesis and Crystal Structure of Anhydrous Analog of 1,25-Dihydroxyvitamin D3

Effect of Vitamin D Conformation on Interactions and Packing in the Crystal Lattice

Dimer and Superstructure of the Active Form of a Vitamin D3. 1.ALPHA.,24(R)Dihydroxy-vitamin D3 Monohydrate, C27O3H44 H2O.

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