Substrates to study the mechanism of vitamin D hydroxylation: synthesis of 25-R-[26-2H3]-cholecalciferol

25-R[26-²H₃]-Cholecalciferol has been synthesised from a C-22 aldehyde derived from egosterol and R-3-[²H₃]-methylbutyl bromide. This vitamin is designed to study the mechanism of enzymic hydroxylation at C-25 in the production of 25S, 26-dihydroxycholecalciferol.     

Convergent and stereoselective synthesis of vitamin D3 via 3,5-cyclovitamins D3

A convergent and stereoselective synthesis of vitamin D₃ was achieved via 3,5-cyclovitamins D₃ (20) which were prepared from the chiral aldehyde (2) and the vinyl bromide (12) derived from Grundmann's ketone.     

An efficient synthesis of 1α, 25-dihydroxy vitamin D3

An efficient synthesis of the title compound is reported based on C-1 functionalization of the triazoline Diels-Alder adduct of 25-OH provitamin D₃ ($\text{2C}$).     

First total synthesis of labeled EPA and DHA-derived A-type cyclopentenone isoprostanoids: [D2]-15-A3t-IsoP and [D2]-17-A4t-NeuroP

A-type cyclopentenone isoprostanoids are abundantly formed in vivo by radical peroxidation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are consumed daily for the prevention of cardiovascular and neurological pathologies. To facilitate in depth studies concerning the effects of these oxidized isoprostanoids on human health, labeled derivatives are necessary. In this paper, we have accomplished the first total synthesis of labeled A-type cyclopentenone isoprostanoids, namely 17,18-[D₂]-15-A_3t-IsoP and 19,20-[D₂]-17-A_4t-NeuroP. The two enantioselective routes are highly convergent, stemming from a common intermediate, readily available by a Julia–Kocienski reaction, and feature the semihydrogenation of an alkyne moiety for the installation of the labeled lower side chain.     

Stereoselective synthesis of (25S)-25-hydroxyvitamin D3 26,23-lactone

Stereoselective synthesis of (25S)-25-hydroxyvitamin D₃ 26,23-lactone ($\text{1w}$) is described starting from C-22 steroidal aldehyde and (S)-citramalic acid. The spectral properties of the compound are almost identical with those of the natural product.     

Synthesis of the dopamine D2/D3 receptor agonist (+)-PHNO via supercritical fluid chromatography: preliminary PET imaging study with [3-C]-(+)PHNO

Carbon-11 labeled (+)-4-[1-¹¹C]propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([1-¹¹C]-(+)-PHNO) is a dopamine D₃-preferring agonist radiopharmaceutical used for medical imaging by positron emission tomography (PET). We report the synthesis of (+)-PHNO using supercritical fluid chromatography for enantiomeric resolution of its norpropyl derivative, HNO, followed by propylation. (+)-HNO was used to prepare the radiolabeling precursor, (+)-trans-4-acetyl-9-triisopropylsilyloxy-2,3,4a,5,6,10b-hexahydro-4H-naphth[1,2b][1,4]oxazine, in 12 steps. Modifications to the labeling procedure were made to ensure consistent preparation of [3-¹¹C]-(+)-PHNO via [¹¹C]CH₃I. A preliminary PET imaging study was carried out with this tracer in an attempt to image dopamine receptors in brown adipose tissue (brown fat) in vivo.     

Selective capture of 1α,25-(OH)2-previtamin D3 utilizing polymer-supported trialkylsilyl triflate in the synthesis of 1α,25-(OH)2-vitamin D3

Catch and release method utilizing polymer-support was investigated in the separation of 1α,25-(OH)₂ pre- and provitamin D₃. Polymer-supported alkyldiisopropylsilyl triflate selectively captured the previtamin D₃ from a 26:74 mixture of pre- and provitamin D₃ produced by photoisomerization of provitamin D₃.     

Synthesis of 24,24-difluoro- and 24ξ-fluoro-25-hydroxyvitamin D3

From cholenic acid 24,24-difluoro-25-hydroxyvitamin D₃ and 24ξ-fluoro-25-hydroxyvitamin D₃ were prepared.     

Synthese von 3-desoxy-3-amino-vitamin D3 und 3-desoxy-3-epiamino-vitamin D3 und D2

Vitamin D₂ and D₃ are transformed with triphenylphosphane-diethylazodicarboxylate-HN₃ into the epimeric azidoderivatives 1 and 3 with inversion of the configuration at C-3. Reduction with LiAlH₄ yields 3-desoxy-3-epiamino-vitamin D₂ and D₃2 and 4, which are characterized as their acetamides 2a and 4a. Furthermore epivitamin D₃-p-nitrobenzoate 5 is produced by reaction of vitamin D₃ with triphenyl- phosphanediethylazodicarboxylate-p-nitrobenzoic acid, which yields epivitamin D₃5a after saponification. Utilizing the same method as above leads with epivitamin D₃ to 5a 3-desoxy-3-azidovitamin D₃6, which is reduced to 3-desoxy-3-amino-vitamin D₃7 by LiAlH₄ and characterized as its acetamide 7a.     

A stereocontrolled partial synthesis of 1α-hydroxy vitamin D3

A novel and efficient partial synthesis of 1α-hydroxy vitamin D₃ ($\text{6}$), starting from 7-dehydrocholesterol ($\text{1}$), is reported. The crucial step in the synthesis involves a selective Diels-Alder reaction of 4-phenyl-1,2,4-triazoline-3,5-dione with the 6,8-diene system of previtamin D₃ ($\text{3}$), generating an adduct $\text{7}$ suitable for the stereoselective introduction of the 1α-hydroxyl group. Cycloreversion of $\text{13}$ leads to the title compound.     

The convenient route to cd fragment for the synthesis of vitamin D3 relatives

The efficient degradation of $\text{1}$ to the α-methylene ketone $\text{4}$ is described. Compound $\text{4}$ was then converted to the allylic alcohol $\text{8a}$ - the precursor of vitamin D³ relatives.     

Stereoselective synthesis of Certonardolsterol D3

The first stereoselective synthesis of Certonardolsterol D₃ was described. Ene reaction and improved allylic oxidation were employed as key steps for efficient construction of the desired 3β,6α,15β-triol steroidal framework. The chiral side chain in Certonardolsterol D₃ was finally introduced by Julia olefination.     

Synthesis of 23,23-difluoro-25-hydroxyvitamin D3

23,23-Difluoro-25-hydroxyvitamin D₃ was synthesized from 6β-methoxy-3α,5-cyclo-23,24-dinor-5α-cholan-22-ol.     

Synthesis of 24,24-difluoro-25-hydroxyvitamin D3

24,24-Difluoro-25-hydroxyvitamin D₃ ($\text{13}$) has been prepared from commercially available lithocholic acid derivative to study the role of 24-hydroxylation in the metabolism of vitamin D₃.     

Depolarized Rayleigh scattering studies of molecular motion of 1,3,4-[D2] thiadiazole

Depolarized Rayleigh scattering spectra have been measured using a Fabry-Pérot interferometer for 1,3,4-[D₂] thiadiazole at temperatures between 20 and 92.5°C, covering a large portion of the liquid and supercooled liquid regions. From the spectral halfwidth measurements, the Rayleigh relaxation times, τ_Ray, have been obtained. A semilog plot of τ_Ray versus T^?1 shows that the data fit well to an Arrhenius equation, with activation energy equal to 2.4 kcal/mole. The relation of τ_Ray to pair orientation correlations is discussed.     

New synthesis of K2[TcF6]

A new high yield synthesis of K₂[⁹⁹TcF₆] is given. It is based on eqn (1) and uses 40% aqueous HF as solvent. [⁹⁹TcBr₆]^2? + 6F^? + 6Ag⁺ → [⁹⁹TcF₆]^2? + 6AgBr (1)