Photosensitized E-Z isomerization of alfa-Calcidol. A photochemical chain reaction

GASTÓN A. ESTRUCH; PEDRO F. ARAMENDÍA

Mendoza

Congreso; 21st IAPS Conference; 2011

IAPS

Biologically and in industry, vitamin D and its derivatives are produced photochemically by pericyclic and photoinduced isomerisation reactions. The first reaction involves the ring aperture in the C9-C10 bond of the 7-dehydrocholesterol, present in animal skin. This ring aperture is followed by photosensitized E-Z isomerisation to produce the biologically active compound for human use. Industrially, the production of hydroxylated vitamin D derivatives, such as Vitamin D3 is a pharmaceutically relevant process, producing high added value products. Precursors are extracts from vegetal origin but bearing mainly an E geometry in the 5,6 double bond. Some years ago, Calverley informed the synthesis of vitamin D3 (5-E-a calcidol) with the correct stereochemistry in the Z 5,6 double bond from the E isomer using anthracene and triethylamine (TEA) as the sensitizer system[1].   Irradiation of E-calcidol with anthracene only in deoxygenated solution yields the Z isomer in a ca 5% yield in the photostationary state. When TEA is added to the system, the E-Z reaction is not inhibited by oxygen any more, the quantum yield of photosiomerization to the Z isomer grows linearly with [E-calcidol], while conversions higher than 90% to the Z isomer are reached in the photostationary state and E-Z quantum yields as high as 45 at [E-calcidol] = 25 mM are reached. If TEA is replaced by DABCO, the reaction rate drops to 1/3 at the same amine concentration. The observations can be explained by the following mechanism, known as quantum chain reaction The high conversion eliminates the need of product purification. Acknowledgements. PFA is a member of CONICET. We thank Delta Biotech (Argentina) for HPLC analysis and for supplying (5-E-a calcidol) [1] M.J.Calverley. Tetrahedron. 43 (1987) 4609-4619.