Synthesis and characterization of bay region halohydrins derived from Benzo[a]pyrene diol epoxide and their role as intermediates in halide-catalyzed cis adduct formation.
Synthesis and characterization of bay region halohydrins derived from Benzo[a]pyrene diol epoxide and their role as intermediates in halide-catalyzed cis adduct formation.
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源自苯并[a]芘二醇环氧化物的湾区卤代醇的合成和表征及其在卤化物催化顺式加合物形成中作为中间体的作用。
DOI：
10.1021/tx980056v
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Meehan,T
中科院分区：
文献类型：
--
作者：
Song,Q;Negrete,GR;Wolfe,AR;Wang,K;Meehan,T
苯并[a]芘的湾区环氧化物（anti-BPDE）烷基化DNA以形成具有>98%反式立体化学的加合物。卤素离子催化该反应;然而，该途径的特征在于形成具有改变的顺式立体化学的加合物。海湾地区卤代醇是这些反应中可能的中间体，但太不稳定而不能从水溶液中分离。然而，我们成功地合成卤代醇在四氢呋喃（THF）中的处理anti-BPDE与相应的卤化锂盐在乙酸的存在下。吸光度和CD光谱清楚地表明氯代、溴代和碘代醇的形成。氯代醇的结构和立体化学由NMR确定。氯化物的加成只发生在环氧化物的苄基位置，C-9和-10位的立体化学是反式的。相对于anti-BPDE的水解产物，氯代、溴代和碘代醇的长波长吸收带分别红移7、13和22 nm。对映体纯卤代醇的圆二色谱中同一吸收带的椭圆率与相应的反BPDE对映体的椭圆率符号相反。这些衍生物的相对稳定性为氯醇>溴醇>碘醇。分离出氯代醇和溴代醇，但碘代醇在此操作过程中分解。加入500 mM氯化物使氯乙醇在50% THF/缓冲液中的水解速率降低4倍。通过吸收光谱法获得了碘乙醇在水性缓冲液/丙酮混合物中瞬时形成的直接证据。在1 M氯化物、溴化物和碘化物存在下，在缓冲水溶液中，抗-BPDE对脱氧腺苷的烷基化反应分别产生85%、91%和92%的顺式加合物。在不存在卤化物的情况下，在缓冲液中脱氧腺苷被抗-BPDE、氯代醇和溴代醇烷基化，分别产生32%、65%和83%的顺式加合物。
The bay region epoxide of benzo[a]pyrene (anti-BPDE) alkylates DNA to form adducts with >98% trans stereochemistry. Halide ions catalyze this reaction; however, this pathway is characterized by the formation of adducts with altered cis stereochemistry. Bay region halohydrins are possible intermediates in these reactions, but are too unstable to be isolated from aqueous solutions. However, we successfully synthesized halohydrins in tetrahydrofuran (THF) by treatment ofanti-BPDE with the corresponding lithium halide salt in the presence of acetic acid. Absorbance and CD spectroscopy clearly indicated the formation of chloro-, bromo-, and iodohydrins. The structure and stereochemistry of the chlorohydrin was established by NMR. Chloride addition is exclusively at the benzylic position of the epoxide, and the stereochemistry of the C-9 and -10 positions is trans. The long-wavelength absorbance band in the chloro-, bromo-, and iodohydrin is red-shifted 7, 13, and 22 nm, respectively, relative to the hydrolysis product ofanti-BPDE. The ellipticity of the same absorbance band in CD spectra of enantiomerically pure halohydrins is opposite in sign compared to that of the correspondinganti-BPDE enantiomer. The relative stability of these derivatives is chlorohydrin > bromohydrin > iodohydrin. The chloro- and bromohydrins were isolated, but the iodohydrin decomposed during this manipulation. The addition of 500 mM chloride decreased the hydrolysis rate of the chlorohydrin 4-fold in 50% THF/buffer. Direct evidence for the transient formation of the iodohydrin in aqueous buffer/acetone mixtures was obtained by absorbance spectroscopy. At 1 M chloride, bromide, and iodide, alkylation of deoxyadenosine byanti-BPDE in aqueous buffer yields 85, 91, and 92% cis adducts, respectively. In the absence of halide, alkylation of deoxyadenosine in buffer byanti-BPDE, the chlorohydrin, and the bromohydrin yields 32, 65, and 83% cis adducts, respectively.