Synthesis of 25-hydroxyvitamin D3-26,23-lactone

All four possible C-23 and C-25 stereoisomers of the title compound have been synthesized. One of these isomers is identical to the natural product.     

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.     

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.     

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 26,26,26-trifluoro-25-hydroxy and 27-nor-26,26,26-trifluoro-25-hydroxyvitamin D3

Two new fluorinated 25-hydroxyvitamin D₃ analogs, 26,26,26-trifluoro- 25-hydroxy ($\text{1}$) and 27-nor-26,26,26-trifluoro-25-hydroxyvitamin D₃ ($\text{2}$), were prepared from 24-phenylsulfonyl 25,26,27-triorcholest-5-en-3β-yl tetrahydropyranyl ether ($\text{3}$).     

New routes to 1α-hydroxyvitamin D3

The sulphone (2) and the methyl ester (3, R=H) were used in stereo-selective syntheses of derivatives of 1α-hydroxyprecalciferol₃ and 1α-hydroxytachysterol₃, which were then converted into the title compound.     

Stereoselective synthesis of (25R)-25,26-dihydroxy-23-oxovitamin D3 and its enzymatic conversion to (25R)-1α,25,26-trihydroxy-23-oxovitamin D3, a putative metabolite of vitamin D3

(25$\text{R}$)-25,26-Dihydroxy-23-oxovitamin D₃ was synthesized efficiently and stereoselectively, and it was converted enzymatically to (25$\text{R}$)-1α,25,26-trihydroxy-23-oxovitamin D₃, a putative metabolite of 1α,25-dihydroxyvitamin D₃. The spectral and chemical properties of (25$\text{R}$)-25,26-dihydroxy-23-oxovitamin D₃ and its 1α,hydroxylated derivative disagree with those reported for the isolated metabolite.     

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.     

Synthesis of 2β-fluoro-1α-hydroxyvitamin D3

2β-Fluoro-1α-hydroxyvitamin D₃($\text{3}$) was prepared from 1,2α-epoxy-cholest-5-en-3β-yl tetrahydropyranyl ether($\text{1a}$ via 2β-fluorocholest-5-ene-1α, 3β-diol($\text{2}$).     

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 ($\text{2C}$).     

Facile and stereoselective synthesis of 25-hydroxyvitamin d2

25-Hydroxyvitamin D₂ as synthesized conveniently and stereoselectively for the first time by utilizing Sharpless' chiral epoxidation and the subsequent regio- and stereoselective methylation with lithium dimethylcuprate to introduce the desired chirality at C(24) and the reductive elimination of the vicinal hydroxy sulfone to introduce stereoselectively the $\text{E}$ double bond at C(22) of the target molecule.     

1-methyl-(D3)-trishomocubane

The acid catalysed rearrangement of 8-methyl-pentacyclo(5.4.0.0^2,6.0^3,10.0^5,9)undecan-8-endo-o1 ($\text{8}$) to 3-methyl-(D₃)-trishomocuban-4-o1 ($\text{9}$) provided the key step to the synthesis of the title compound ($\text{11}$).     

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.     

Stereoselective synthesis of conformationally constrained (2S,3S)-3-hydroxyornithine

A convenient and efficient route is described for the highly stereoselective synthesis of δ-amino protected and conformationally restricted (2S,3S)-3-hydroxyornithine through the N-benzylnitrone adduct to the α,β-unsaturated bicyclic lactam 2 derived from (S)-pyroglutaminol.     

Stereoselective synthesis of (S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile

(S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile (1) is a key intermediate in the preparation of PF-00951966, (1) a fluoroquinolone antibiotic for use against key pathogens causing community-acquired respiratory tract infections including multidrug resistant (MDR) organisms. The current work describes the development of a highly efficient and stereoselective synthesis of 1 in 10 steps with an overall yield of 24% from readily available benzyloxyacetyl chloride. Two key transformations in the synthetic sequence involve (a) catalytic asymmetric hydrogenation with chiral DM-SEGPHOS-Ru(II) complex to afford β-hydroxy amide 11b in good yield (73%) and high stereoselectivity (de 98%, ee >99%) after recrystallization and (b) S(N)2 substitution reaction with methylamine to provide diamine 14 with inversion of configuration at the 1'-position in high yield (80%), after efficient purification using a simple acid/base extraction protocol.