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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, United States.
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, United States.
authors.forename: Zongtao
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
authors.forename: Tae-Kang
authors.initials: TK
authors.lastname: Kim
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Veteran Affairs Medical Center, Birmingham, AL 35294, United States.
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, United States.
authors.forename: Duane D
authors.initials: DD
authors.lastname: Miller
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, United States. Electronic address: wli@uthsc.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002112:Calcifediol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma / Q000473:pathology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: C480634:20-hydroxyvitamin D3; D000970:Antineoplastic Agents; D002117:Calcitriol; D002112:Calcifediol
keywords: 20S-Hydroxyvitamin D3; PCR; Reporter assay; Thymidine incorporation; Total chemical synthesis; VDR activation