Synthesis of (+/-)-trans-7,8-dihydroxy-6-fluoro-7,8-dihydrobenzo[a]pyrene, the metabolite from 6-fluoro-benzo[a]pyrene, is described. Position 6 of 7,8,9,10-tetrahydrobenzo[a]pyren-7-ol (1) was functionalized by bromination with N-bromosaccharin. Regioselectivity in the bromination is thought to derive from a substrate-reagent hydrogen bond. NMR evidence is offered to support this model. The 6-bromo derivative 2 was subjected to dehydration followed by bromine-lithium exchange. Quenching the lithio intermediate with NFSi afforded the 6-fluoro derivative 4. Prévost reaction on the 7,8 double bond resulted in the trans dibenzoate 5 (established by comparison to a cis derivative prepared by osmium tetroxide cis dihydroxylation). Introduction of the 9,10 double bond by a bromination-dehydrobromination procedure, followed by hydrolysis, gave racemic trans-7,8-dihydrodiol 7. Resolution of the enantiomers was achieved by chiral HPLC, and the absolute configurations of the early and late eluting isomers were determined through CD spectroscopy by comparison with the metabolically obtained (7R,8R)-dihydrodiol.

中文翻译：

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通过取代的P的羟基定向的区域选择性官能化合成6-氟-苯并[a] py的（+/-）-反式-7,8-二氢二醇。

描述了（+/-）-反式-7,8-二羟基-6-氟-7,8-二氢苯并[a] py的合成，该代谢物是由6-氟-苯并[a] py制成的。通过用N-溴糖精溴化，将7,8,9,10-四氢苯并[a] py-7-醇（1）的6位官能化。认为溴化中的区域选择性源自底物-试剂氢键。提供了NMR证据来支持该模型。对6-溴衍生物2进行脱水，然后进行溴-锂交换。用NFSi淬灭硫代中间体，得到6-氟衍生物4。在7，8双键上的Prévost反应产生反式二苯甲酸酯5（通过与通过四氧化顺式二羟基化制备的顺式衍生物比较而建立）。通过溴化-脱氢溴化程序引入9,10双键，然后进行水解，