Synthesis and photo-conversion of androsta- and pregna-5,7-dienes to vitamin D3-like derivatives

Michal A. Zmijewski, Wei Li, Jordan K. Zjawiony, Trevor W. Sweatman, Jianjun Chen, Duane Miller, Andrzej T. Slominski

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Calcitriol (3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-1α, 3β,25-triol) is a powerful oncostatic form of vitamin D3 that is of limited clinical utility due to hypercalcemic (toxic) effects. Since the removal of the side chain reduces or eliminates the calcemic activity of vitamin D3, secosteroidal compounds lacking or with a shortened side chain are good candidates for anti-cancer drugs. In addition, 5,7-steroidal dienes without a side chain can be generated in vivo under pathological conditions. A series of androsta- and pregna-5,7-dienes was efficiently synthesized from their respective 3-acetylated 5-en precursors by bromination-dehydrobromination and deacetylation reactions. Ultraviolet B (UVB) irradiation was used to generate corresponding 9,10-secosteroids with vitamin D-like structures. Additional products with tachysterol-like (T-like) structures or 5,7-dienes with inverted configuration at C-9 and C-10 (lumisterol, L-like) were also detected. Different doses of UVB resulted in formation of various products. At low doses, previtamin D-, T- or L-like compounds were formed as the main products, while higher doses induced further isomerization, with formation of potentially oxidized derivatives. In summary, we describe dynamic UVB induced conversion of androsta- and pregna-5,7-dienes into vitamin D-like compounds and their rearranged analogues; additionally novel T-like and L-like structures were also produced and characterized. Further biological evaluation of newly synthesized compounds should help to select the best candidate(s) for potential treatment of hyperproliferative diseases including cancer.

Original languageEnglish (US)
Pages (from-to)1570-1576
Number of pages7
JournalPhotochemical and Photobiological Sciences
Volume7
Issue number12
DOIs
StatePublished - Dec 3 2008

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vitamins
Cholecalciferol
dienes
Vitamin D
Secosteroids
calciferol
Trientine
Derivatives
Ergosterol
Calcitriol
Poisons
synthesis
Isomerization
dosage
products
cancer
triols
Irradiation
bromination
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry

Cite this

Synthesis and photo-conversion of androsta- and pregna-5,7-dienes to vitamin D3-like derivatives. / Zmijewski, Michal A.; Li, Wei; Zjawiony, Jordan K.; Sweatman, Trevor W.; Chen, Jianjun; Miller, Duane; Slominski, Andrzej T.

In: Photochemical and Photobiological Sciences, Vol. 7, No. 12, 03.12.2008, p. 1570-1576.

Research output: Contribution to journalArticle

Zmijewski, Michal A. ; Li, Wei ; Zjawiony, Jordan K. ; Sweatman, Trevor W. ; Chen, Jianjun ; Miller, Duane ; Slominski, Andrzej T. / Synthesis and photo-conversion of androsta- and pregna-5,7-dienes to vitamin D3-like derivatives. In: Photochemical and Photobiological Sciences. 2008 ; Vol. 7, No. 12. pp. 1570-1576.
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