Total synthesis of biologically active 20S-hydroxyvitamin D3

Qinghui Wang; Zongtao Lin; Tae Kang Kim; Andrzej T. Slominski; Duane D. Miller; Wei Li

doi:10.1016/j.steroids.2015.09.009

Total synthesis of biologically active 20S-hydroxyvitamin D3

Qinghui Wang
, Zongtao Lin
, Tae Kang Kim
, Andrzej T. Slominski
, Duane D. Miller
, Wei Li

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

A total synthetic strategy of 20S-hydroxyVitamin D3 [20S-(OH)D3] involving modified synthesis of key intermediates 7 and 12, Grignard reaction to stereoselectively generate 20S-OH and Wittig-Horner coupling to establish D3 framework, was completed in 16 steps with an overall yield of 0.4%. The synthetic 20S-(OH)D3 activated Vitamin D receptor (VDR) and initiated the expression of downstream genes. In addition, 20S-(OH)D3 showed similar inhibitory potency as calcitriol [1,25(OH)₂D3] on proliferation of melanoma cells.

Original language	English
Pages (from-to)	153-162
Number of pages	10
Journal	Steroids
Volume	104
DOIs	https://doi.org/10.1016/j.steroids.2015.09.009
State	Published - Dec 1 2015

Keywords

20S-Hydroxyvitamin D3
PCR
Reporter assay
Thymidine incorporation
Total chemical synthesis
VDR activation

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10.1016/j.steroids.2015.09.009

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title = "Total synthesis of biologically active 20S-hydroxyvitamin D3",

abstract = "A total synthetic strategy of 20S-hydroxyVitamin D3 [20S-(OH)D3] involving modified synthesis of key intermediates 7 and 12, Grignard reaction to stereoselectively generate 20S-OH and Wittig-Horner coupling to establish D3 framework, was completed in 16 steps with an overall yield of 0.4\%. The synthetic 20S-(OH)D3 activated Vitamin D receptor (VDR) and initiated the expression of downstream genes. In addition, 20S-(OH)D3 showed similar inhibitory potency as calcitriol [1,25(OH)2D3] on proliferation of melanoma cells.",

keywords = "20S-Hydroxyvitamin D3, PCR, Reporter assay, Thymidine incorporation, Total chemical synthesis, VDR activation",

author = "Qinghui Wang and Zongtao Lin and Kim, \{Tae Kang\} and Slominski, \{Andrzej T.\} and Miller, \{Duane D.\} and Wei Li",

note = "Funding Information: This work was supported by NIH grants 1R21AR063242-01A1 (W.L. and D.D.M.), 1S10OD010678-01 (W.L.), 1S10RR026377-01 (W.L.), 2R01AR052190 -(A.S.) and R21AR066505-01A1 (A.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ",

year = "2015",

month = dec,

day = "1",

doi = "10.1016/j.steroids.2015.09.009",

language = "English",

volume = "104",

pages = "153--162",

journal = "Steroids",

issn = "0039-128X",

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TY - JOUR

T1 - Total synthesis of biologically active 20S-hydroxyvitamin D3

AU - Wang, Qinghui

AU - Lin, Zongtao

AU - Kim, Tae Kang

AU - Slominski, Andrzej T.

AU - Miller, Duane D.

AU - Li, Wei

N1 - Funding Information: This work was supported by NIH grants 1R21AR063242-01A1 (W.L. and D.D.M.), 1S10OD010678-01 (W.L.), 1S10RR026377-01 (W.L.), 2R01AR052190 -(A.S.) and R21AR066505-01A1 (A.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - A total synthetic strategy of 20S-hydroxyVitamin D3 [20S-(OH)D3] involving modified synthesis of key intermediates 7 and 12, Grignard reaction to stereoselectively generate 20S-OH and Wittig-Horner coupling to establish D3 framework, was completed in 16 steps with an overall yield of 0.4%. The synthetic 20S-(OH)D3 activated Vitamin D receptor (VDR) and initiated the expression of downstream genes. In addition, 20S-(OH)D3 showed similar inhibitory potency as calcitriol [1,25(OH)2D3] on proliferation of melanoma cells.

AB - A total synthetic strategy of 20S-hydroxyVitamin D3 [20S-(OH)D3] involving modified synthesis of key intermediates 7 and 12, Grignard reaction to stereoselectively generate 20S-OH and Wittig-Horner coupling to establish D3 framework, was completed in 16 steps with an overall yield of 0.4%. The synthetic 20S-(OH)D3 activated Vitamin D receptor (VDR) and initiated the expression of downstream genes. In addition, 20S-(OH)D3 showed similar inhibitory potency as calcitriol [1,25(OH)2D3] on proliferation of melanoma cells.

KW - 20S-Hydroxyvitamin D3

KW - PCR

KW - Reporter assay

KW - Thymidine incorporation

KW - Total chemical synthesis

KW - VDR activation

UR - https://www.scopus.com/pages/publications/84947926151

U2 - 10.1016/j.steroids.2015.09.009

DO - 10.1016/j.steroids.2015.09.009

M3 - Article

C2 - 26433048

AN - SCOPUS:84947926151

SN - 0039-128X

VL - 104

SP - 153

EP - 162

JO - Steroids

JF - Steroids

ER -

Total synthesis of biologically active 20S-hydroxyvitamin D3

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Keywords

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