Synthesis and photo-conversion of androsta- and pregna-5,7-dienes to vitamin D3-like derivativesThis paper was published as part of the themed issue in honour of Nicholas Turro.Electronic supplementary information (ESI) available: HPLC chromatogram, UV spectra and additional experimental data for irradiation products of androsta- and pregna-5,7-dienes. NMR spectra for 5a, 5aD, 5aLand 5aTand Table of shifts for androsta- and pregna-5,7-dienes. See DOI: 10.1039/b809005j

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 vivounder 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. [ABSTRACT FROM AUTHOR]