tBu HOCPha

Scheme 17

tBu HOCPha tBu (41)

tBu tBu

Scheme 18

2.1.4 Glucocorticosteroids. These products show, among other effects, an important anti-inflammatory activity. It is known that they have to be protected from light, and their photoreactivity has been explored both in solution and in the solid state. Hydrocortisone (49), cortisone (50) and their acetates (51, 52) undergo photo-oxidation in the solid state; the main process involves loss of the side-chain at C(17) to give androstendione and trione derivatives respectively (Scheme 19).58 Molecular packing has an important role in determining the photostability in the solid. As an example, irradiation of crystalline hydrocortisone tert-butylacetate leads to photo-oxidation (to give the corresponding cortisone) for two out of five of the polymorphs investigated, while the other ones are photostable. This fact has been correlated with the possibility of oxygen to penetrate in the crystal in such structures.59





Scheme 19

Cross-conjugated glucocorticosteroids such as prednisolone, prednisone, bethmetasone, triamcinolone and others are quite photoreactive, as one may expect since the efficient photorearrangement of cyclohexadienones to bicyclo[3.1.0]hexenones is well known.60 This rearrangement has been observed for prednisone (53),61 prednisolone (54),62 dexamethasone (55) 63,64 betamethasone (56) and some of their acetates (see Scheme 20).65'66 The primary photoproducts may undergo further transformation with cleavage of the three-membered ring, resulting in rearomatisation or cleavage of ring A or in expansion of ring B according to conditions.

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