| 摘要 |
<p>Prodn. of 5-methoxy-psoralene (I) comprises (a) methylation of phloroglucinol (II) using methanol and a current of gaseous HCl to give a mixt. of the mono- and di-methyl ethers and isolation of the monomethyl ether by fractional distn. (b) cyclisation of phloroglucinol mono-methylether with chloro-acetonitrile, zinc chloride, a current of gaseous HCl and potassium acetate to yield 6-hydroxy-4-methoxy-coumaran-3-one (III), (c) redn. of (III) with hydrazine hydrate and KOH to yield 6-hydroxy-4-methoxy-coumarone (IV), (d) cyclisation of (IV) with acrylonitrile, zinc chloride and gaseous HCl to give 3,4,4',5'-tetrahydro-5-methoxypsoralene (V) and (e) dehydrogenation of (V) to give (I). Used in treatment of psoriasis and dermatoses such as vitiligo(leukoderma), a typical eczema and fungal mycosis. (I) is administered orally, in doses of 40-300 mmg(pref. 60-150 mmg), or topically using compsns. containing 100-1000 ppm of (I) and is activated by irradiation with ultraviolet. The activity of (I) (as measured by its phototoxicity) is only about 25% less than the activity of currently used 8-methoxy-psoralene whilst its acute toxicity is much less (17x) giving it a superior therapeutic index. Prepn. uses economic starting cpds. contains less stages than known processes, uses a readily available redn. catalyst which avoids ageing and regeneration problems and gives good yields.</p> |
