The role of substrate structure in the initiation of enzymic cyclization of squalene 2,3-oxide. Studies with 2,3-cis-1'-norsqual ene 2,3-oxide and 2,3-trans-1'-norsqualene 2,3-oxide.
The role of substrate structure in the initiation of enzymic cyclization of squalene 2,3-oxide. Studies with 2,3-cis-1'-norsqual ene 2,3-oxide and 2,3-trans-1'-norsqualene 2,3-oxide.
复制标题
底物结构在角鲨烯 2,3-氧化物酶环化引发中的作用。
DOI：
10.1021/ja01005a065
复制
发表时间：
1968
影响因子：
15
通讯作者：
R. Nadeau
中科院分区：
文献类型：
--
作者：
R. B. Clayton;E. E. van Tamelen;R. Nadeau
角鲨烯2，3-氧化物（I）通过一种由人肝微粒体酶系统环化为羊毛甾醇（II），1-4和角鲨烯2，3-氧化物类似物（在分子的末端6 -6和更中心的7部分被修饰）也通过该酶系统环化。角鲨烯2，3-氧化物分子在氧化环附近的结构修饰对酶促环化反应的起始具有很强的电子效应和空间效应。这些效应的探索可能阐明酶-底物相互作用的特点，支配这个初始阶段的环化。因此，我们将2，3-顺式-和2，3-反式-l ′-去甲角鲨烯2，3-氧化物（IIIa，B）进行环化酶系统的作用，并发现只有2，3-反式-氧化物III B产生4-去甲基羊毛甾醇类似物（4，14 α-二甲基-Δ 8 -2 4-胆甾二烯-3/3-醇，IV）.2，3-顺式-和2，3-反式-l '-去甲角鲨烯2，3-氧化物（伊利亚和IIIb）由[4- 3 H] 1，1 '，2-三降-角鲨烯-3-羧酸酯8通过与二乙基锍乙基化物反应制备。通过在硅胶上用3% EtOAc-己烷重复连续分离2.5小时，将更移动的反式异构体与顺式异构体分离。伊利亚和IIIb用HCl O 4-H2O得到相应的二醇Va和Vb，得到相应的纯丙酮化物Via和VIb。与氧化物不同，这些化合物在Carbowax柱上对glpc 11稳定，Rc为1.71（Via）和2.03（VIb）。
Squalene 2, 3-oxide (I) is cyclized to lanosterol (II) by a microsomal enzyme system of mammalianliver, 1-4 and squalene 2, 3-oxide analogs, modifiedin the termi-nal6-6 and more central7 portions of the molecule, are also cyclized by this enzyme system. Structural modi-fications of the squalene 2, 3-oxide molecule in the proximity of the oxide ring should exert strong elec-tronic and steric effects upon the initiation of enzymic cyclization. Exploration of these effectsmay elucidate features of enzyme-substrate interaction that govern this initial phase of cyclization. We have therefore subjected 2, 3-cis-and 2, 3-trans-l'-norsqualene 2, 3-oxides (IIIa, b) to the action of the cyclase system and have found that only the 2, 3-trans-oxide Illb yields a 4-desmethyllanosterol analog (4, 14a-dimethyl-A8-2 4-cholestadien-3/3-ol, IV).2, 3-cis-and 2, 3-trans-l'-norsqualene 2, 3-oxides (Ilia and Illb) were prepared from [4-3H] 1, 1', 2-trisnor-squalene-3-carboxaldehyde8 by reaction with diethylsulfonium ethylide. 9 The more mobile trans isomer was separated from the cis by repeated continuous tic10 on silica gel with 3% EtOAc-hexane for 2, 5 hr. Ilia and Illb, with HCIO4-H2O, gave the corresponding glycols Va and Vb which afforded the corresponding pure acetonides Via and VIb. These, unlike theoxides, were stable on glpc11 on columns of Carbowax, with Rc 1.71 (Via) and 2.03 (VIb).