General patterns in the photochemistry of pregna-1,4-dien-3,20-diones.
The photochemistry of six pregna-1,4-dien-3,20-diones has been compared and found to involve both the cyclohexadienone moiety in ring A and the isolated ketone at C-20. The two reactions take place proportionally to the fraction of light absorbed by each chromophore. The cross-conjugated ketone absorbs predominantly or exclusively at both 254 and 366 nm and undergoes the "lumi" rearrangement to bicyclo[3.1.0]hex-3-en-2-one. The quantum yield of the reaction diminished somewhat with increasing lambda(exc), e.g., for prednisolone Phi(254) (nm) = 0.42, Phi(366) (nm) = 0.3. A much stronger lowering is caused by halogen substitution in position 9 (by a factor of 3 for F, >50 for Cl), apparently due to a shortened triplet lifetime caused by heavy atom effect. At 310 nm, both chromophores absorb to a comparable degree and both may react. The reaction at C(20) ketone involves either quite efficient alpha-cleavage (C(17)-C(20)) for compounds bearing an acetal or hydroxyl function at C(17) or less effective (by a factor of ca. 10) hydrogen abstraction from the 18-methyl group in the other cases (finally resulting in Norrish II fragmentation or Yang cyclization). The results allow generalizing how the substitution pattern surrounding each chromophore affects the photoreactivity at that site and the competition between the two modes, allowing predicting the photochemistry of this family of antiinflammatory drugs.
Ricci
Andrea
A
Dep. Organic Chemistry, University of Pavia, Via Taramelli 10, Italy.
Fasani
Elisa
E
Mella
Mariella
M
Albini
Angelo
A
D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000528:radiation effects; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D015394:Molecular Structure; D010777:Photochemistry; D011239:Prednisolone / Q000737:chemistry; D011245:Pregnadienes / Q000737:chemistry* / Q000528:radiation effects
D000893:Anti-Inflammatory Agents; D011245:Pregnadienes; D011239:Prednisolone