General Patterns in the Photochemistry of Pregna-1,4-dien-3,20-diones

Abstract

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.

Photochemistry of Desonide, a Non-fluorinated Steroidal Anti-inflammatory Drug

“…This lead to a different photochemistry observed by the direct excitation of ketone chromophore. Albini et al 8,9) have demonstrated non-communicating reaction paths in some pregna-1,4-diene-3,20-dione. Since many steroidal drugs are commonly used and several reports on their phototoxic effects have been reported, [10][11][12][13] it was of interest to extensively study the aspect of competition between chemical reactions of the separated excited moieties incorporated in the rigid skeleton of the steroids.…”

Photostability of Topical Agents Applied to the Skin: A Review

“…Glucocorticosteroids pregna-1,4-dien-3,20-diones [24] betamethasone and its esters [25,26] betamethasone-17 valerate [27] mometasone furoate [28] hydrocortisone 21-acetate [29] prednisolone [30] fluocinolone 16,17-acetonide [31,32] desonide [33,34] Retinoids vitamin A [35] tretinoin [36][37][38][39][40][41][42][43][44] isotretinoin [36,37,45] adapalene [46,47] tazarotene [48] Antifungal drugs clotrimazole [49,50] bifonazole [51] itraconazole [52,53] terbinafine [54] Non-steroidal antiinflammatory drugs piroxicam [55][56][57] naproxen [58][59][60][61] diclofenac [57,58,62] ketoprofen [63][64][65][66] ibuprofen …”

In vitro and in vivo evaluation of a desonide gel-cream photostabilized with benzophenone-3

“…This reaction was reported for prednisolone, whose spectrum and k max (242 nm) are similar to desonide. In some cases, another possible reaction involves the cleavage of C17ÀC20 or the hydrogen abstraction from the 18-methyl group 39 . According to Moore 40 , the spectrum of a drug molecule is usually broad, and any overlap of the absorption spectrum with the output of the photon source colliding with it has the potential to start the photochemical change.…”