H

cl7fVNvTCHGb hv >

H2NO2S^SO.NH (134) H20 H2N02S

Scheme 40

2.3.5 Serum Lipid Reducing Agents and Antithrombotic Agents. The antihyperlipoproteinemic drug fenofibrate (136) is photolabile under aerobic conditions, yielding peracid (137) among other compounds (scheme 41).148 Several other drugs of this group [gemfibrozil (138), bezafibrate (139), clofibric acid (140) and clofibrate (141)] have also been found to be oxidatively photodegraded.149 Thyroxine (142), the D form of which is used as antihyperlipoproteinemic, is rapidly photodeiodinated. Initial reaction involves the iodine atom ortho to the phenoxy function, and then the reaction proceeds stepwise to give 3-iodothyronine, the fourth iodine being more resistant to elimination.150

0(CH2)3CMe2C02H (138)

0(CH2)3CMe2C02H (138)

Cl-^jy-CONH(CH2)2

0CMe2C02H (139)

ClYrj)V0CMe2C02R

0CMe2C02H (139)

The anticoagulant dipyridamole (143), a pteridine derivative, undergoes oxidation of one of the piperidine side chains giving (144) upon irradiation in solution.151 Another anticoagulant, warfarin sodium (145), has been found to be photostable in the solid state.152 The photochemistry of vitamins K is discussed in Sec. 2.7.1.

2.4 Gonadotropic Steroids and Synthetic Estrogens

When irradiated in buffered (pH 7.4) aqueous solution the progestinic norethisterone (146a, R=Me, R-H) (Scheme 42) is photo-oxidised to give the 4,5-epoxide (147a) ((5,3 diastereoisomer predominating) and the 5-hydroxy (148a) (a epimer predominating) derivatives as well as photo-dimerised.153-155 The phenolic ring present in estrogens makes these substrates quite labile to photo-oxidation. The reaction can be conveniently carried out by photosensitisation, under conditions where singlet oxygen is produced avoiding direct irradiation of the substrate. Thus, the photosensitised reaction of ethinyl estradiol (149) in solution involves addition of singlet oxygen to the electron rich phenolic ring to yield a the ketohydroperoxide (150) (Scheme 43).156 Estrone (151) reacts similarly (Scheme 43).157 A9(11)-dehydroestrone (152) gives complex mixture of products upon photosensitised oxygenation, while the corresponding methyl ether (153) undergoes clean cleavage of the C ring to give the ketoaldehyde (154) (Scheme 44).158>159

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