Synthesis and biological characterization of 1α,24,25-trihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (24-hydroxylated ED-71)

Hatakeyama, Susumi; Kawase, Akira; Uchiyama, Yasushi; Maeyama, Junji; Iwabuchi, Yoshiharu; Kubodera, Noboru

doi:10.1016/s0039-128x(00)00149-5

Cited by 22 publications

(7 citation statements)

References 17 publications

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“…The syntheses of the pairs 2a , 2b and 3a , 3b were achieved by two different routes as indicated in Scheme . The sequence of steps leading to 2a and 2b involves an elaborate functional-group protection strategy, previously established, with the aim to ensure the integrity of the trans -octahydroindene ring juncture. This sequence, illustrated in Scheme for the synthesis of 2a and 2b , commenced with the conversion of diol 6 18 to the iodo alcohol 8 followed by iodide displacement with sodium benzenesulfinate.…”

Section: Synthetic Methodsmentioning

confidence: 99%

Calcitriol Derivatives with Two Different Side Chains at C-20. II. Diastereoselective Syntheses of the Metabolically Produced 24(R)-Hydroxygemini

Maehr¹,

Uskoković²,

Adorini³

et al. 2004

J. Med. Chem.

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Vitamin D derivatives containing two side chains emanating at C-20 are known as gemini. We have recently synthesized two gemini which are related to calcitriol and 19-norcalcitriol containing two identical side chains. The metabolism of these species involves 24(R)-hydroxylation on one of the side chains. To determine the outcome of this diastereospecific transformation, we synthesized both C-20 epimeric pairs containing the 24(R)-hydroxy group in the gemini and 19-norgemini series. On the basis of the availability of these reference compounds, it was shown that the metabolic hydroxylation occurred at the pro-R side chain in both gemini compounds. In comparison to the parent compounds, the 24-hydroxygemini required higher doses to increase blood calcium levels in mice and to suppress INF-gamma release in MLR.

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Section: Synthetic Methodsmentioning

confidence: 99%

Calcitriol Derivatives with Two Different Side Chains at C-20. II. Diastereoselective Syntheses of the Metabolically Produced 24(R)-Hydroxygemini

Maehr¹,

Uskoković²,

Adorini³

et al. 2004

J. Med. Chem.

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“…The mixture was filtered, and the filtrate was concentrated at 30−40 °C under vacuum. The resulting residue was added MTBE (20 L) and stirred for 1 h. The suspension was filtered, and the filtrate was purified by silica gel chromatography (n-heptane/EtOAc = 100:1−50:1) to give the colorless oil product 17 (3R,4R,5R)-4-(3-((tert-Butyldiphenylsilyl)oxy)propoxy)-3-((tert-butyldimethyl silyl)oxy)-9-((tetrahydro-2H-pyran-2-yl)oxy)-non-1-en-7-yn-5-ol (19). To a solution of 18 (153 g, 1.09 mol) in THF (1.53 L) was added n-butyllithium solution in n-hexane (0.5 L, 5.1 mol) dropwise at −60 °C and stirred for 0.5 h. A solution of 17 (200 g, 0.370 mol) in THF (0.57 L) and BF 3 •Et 2 O (50 mL) was added successively at −60 °C.…”

Section: (2r3s4r)-4-((tert-butyldimethylsilyl)oxy)-3-(3-((tertbutyldi...mentioning

confidence: 99%

“…However, the stereoselective construction of the A-ring fragment represented a formidable challenge, several of which are shown in Figure . One synthetic route to the A-ring (12 steps, 10.4%) eneyne fragment started from a symmetrical epoxide 1 (obtained by (−)-diethyl d -tartrate, five steps, 65.4%), in which several different types of C–C elongation, cyclization, and redox reactions were involved. − ,− Although the overall yield is acceptable, this route lacks the ability to construct the stereocenter at the C-1 position of the A-ring, leading to purification difficulties.…”

Section: Introductionmentioning

confidence: 99%

Novel, Practical, and Scalable Approach for the Synthesis of Eldecalcitol

Chen

Tan

Jiang³

et al. 2023

Org. Process Res. Dev.

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A novel, practical, and scalable approach for the synthesis of eldecalcitol (2), via the Horner–Wadsworth–Emmons (HWE) olefination of A-ring and C/D-ring fragments, has been described. The improved route was carried out to produce the key intermediate chiral epoxide 17 in good yield (13 steps, 9.0% overall yield) and high optical purity based on the utilization of d-mannose as a readily accessible, economically attractive chiral raw material. This process employed d-mannose as the chiral pool to directly assemble all the stereocenters of the A-ring fragment, thereby reducing the complexity of the chiral separation process, eliminating the need for asymmetric oxidation required for the construction of the C-3 stereocenter, and ultimately increasing the efficiency.

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“…A following condensation with the 2-oxiranyl-2-propanol, prepared in situ from 12 [13] to diol 13 as an epimeric mixture which was subjected to reductive de-sulfonylation and de-silylation to furnish the tetraol 14. The vicinal diol was protected as the oxolane 15, and then oxidized with pyridinium dichromate to ketone 16.…”

Section: Syntheses Of 124(r)25-trihydroxy-21-(3-hydroxy-3-methyl-bumentioning

confidence: 99%

Calcitriol derivatives with two different side chains at C-20

Maehr¹,

Uskoković²,

Reddy³

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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Synthesis and biological characterization of 1α,24,25-trihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (24-hydroxylated ED-71)

Cited by 22 publications

References 17 publications

Calcitriol Derivatives with Two Different Side Chains at C-20. II. Diastereoselective Syntheses of the Metabolically Produced 24(R)-Hydroxygemini

Calcitriol Derivatives with Two Different Side Chains at C-20. II. Diastereoselective Syntheses of the Metabolically Produced 24(R)-Hydroxygemini

Novel, Practical, and Scalable Approach for the Synthesis of Eldecalcitol

Calcitriol derivatives with two different side chains at C-20

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