UNIFIED STRATEGY FOR SYNTHESIS OF INDOLE AND 2-OXINDOLE ALKALOIDS
UNIFIED STRATEGY FOR SYNTHESIS OF INDOLE AND 2-OXINDOLE ALKALOIDS
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DOI：
10.1021/ja00016a036
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发表时间：
1991-07-31
影响因子：
15
通讯作者：
MORTIMORE, M
中科院分区：
文献类型：
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作者：
MARTIN, SF;BENAGE, B;MORTIMORE, M
利用分子内Diels-Alder反应构建目标生物碱的D/E环亚单位的策略，开发了一种简明而通用的具有代表性的吲哚生物碱类化合物的条目，这些生物碱包括yohimboid类、杂ohimboid类、corynantheid和2-oxindole类。该方法的有效性首先通过从22经两步全合成育亨氏生物碱氧甘草单宁(2)来说明。因此，通过将乙烯基酮缩醛24与22与23反应而原位生成的中间体N-酰亚胺盐进行亲核加成而制备的Diels-Alder底物25在苯醌的存在下被加热，以得到非对映异构体环加成物26和27的混合物；这些加合物经过自发氧化得到2。在该策略的另一应用中，34a的[4+2]杂环化反应是通过将1-[(三甲基硅氧基)氧基]丁二烯亲核加成到由22与巴豆酰氯处理后原位生成的N-酰基丁二烯盐而形成的，从而提供了加成物35a和36a的混合物(约9：1)。主要加合物35a通过影响烯醇醚的β-甲氧基化得到乙烯基碳酸酯的一般程序被转化为42a。随后，通过选择性地传递2或1当量的氢化物，将42a还原为杂环生物碱(+/-)-四氢阿尔斯通(3)和(+/-)-氨基己胺(4)。42a经酰胺处理后，经立体选择性β-消除反应得到49个，经化学选择性氢化物还原转化为鸡冠花碱(+/-)-吉西西嗪(5)。通过使用一种新的方案实现了β-咔啉N(B)内酰胺类化合物的立体选择性氧化重排为3，3-二取代的2-氧吲哚，从而实现了对2-氧吲哚家族生物碱的简便获取。因此，42a暴露于次氯酸叔丁酯，然后酸和银离子诱导中间体3-氯吲哚的重排得到50，只有微量的C(7)同分异构体被检测到。50的氢化物还原得到(+/-)-异喋啶(6)，酸催化的异构化提供了6和(+/-)-蝶啶(51)的平衡混合物(1：3)。计算分析了34a分子内杂化Diels-Alder反应得到35a和36a作为唯一可分离的环加合物的立体化学过程。用半经验方法建立了六原子过渡态的几何构型，采用标准的闭壳受限Hartree-Fock(RHF)AM1方法。通过对六元周环阵列使用这种受约束的几何结构，四个可能的过渡态52-55的总构象能量通过MM2计算(MacroModel)最小化。计算得到的这些过渡态的相对能量为52<；53&54<；55。由于34a的环化只通过相应的过渡态52和53以大约9：1的比例产生35a和36a，这些计算与实验结果定性地关联。
A concise and general entry to representative indole alkaloids of the yohimboid, heteroyohimboid, corynantheoid, and 2-oxindole classes has been developed exploiting a strategy that features intramolecular Diels-Alder reactions for the facile construction of the D/E ring subunits of the target alkaloids. The efficacy of the approach is first illustrated by a two-step total synthesis of the yohimboid alkaloid oxogambirtannine (2) from 22. Thus, the Diels-Alder substrate 25, which was prepared by nucleophilic addition of vinyl ketene acetal 24 to the intermediate N-acyliminium salt formed in situ upon reaction of 22 with 23, was heated in the presence of benzoquinone to give a mixture of diastereoisomeric cycloadducts 26 and 27; these adducts underwent spontaneous oxidation to furnish 2. In another application of the strategy, the [4 + 2] heterocyclization of 34a, which was formed upon nucleophilic addition of 1-[(trimethylsilyl)oxy]butadiene to the N-acyliminium salt generated in situ upon treatment of 22 with crotonyl chloride, afforded a mixture (ca. 9:1) of cycloadducts 35a and 36a. The major adduct 35a was converted to 42a using a general procedure for effecting beta-carbomethoxylation of enol ethers to give vinylogous carbonates. Subsequent reduction of 42a to the heteroyohimboid alkaloids (+/-)-tetrahydroalstonine (3) and (+/-)-cathenamine (4) was achieved by selective delivery of 2 or 1 equiv of hydride, respectively. When 42a was treated with sodium amide, stereoselective beta-elimination ensued to give 49, which was converted by chemoselective hydride reduction into the corynantheoid alkaloid (+/-)-geissoschizine (5). Facile access to alkaloids of the 2-oxindole family was realized by using a new protocol for achieving stereoselective, oxidative rearrangements of beta-carboline N(b) lactams into 3,3-disubstituted 2-oxindoles. Thus, exposure of 42a to tert-butyl hypochlorite followed by acid and silver ion induced rearrangement of the intermediate 3-chloroindolenine gave 50, with only traces of the C(7) epimer being detected. Hydride reduction of 50 gave (+/-)-isopteropodine (6), acid-catalyzed isomerization of which furnished an equilibrium mixture (1:3) of 6 and (+/-)-pteropodine (51). The stereochemical course of the intramolecular hetero-Diels-Alder reaction of 34a to give 35a and 36a as the only isolable cycloadducts was examined by computational analysis. The geometry of the six-atom transition state was established by semiempirical methods by using the standard closed-shell, restricted Hartree-Fock (RHF) version of the AM1 method. With use of this constrained geometry for the six-membered pericyclic array, the overall conformational energies for the four possible transition states 52-55 were minimized by MM2 calculations (MacroModel). The calculated relative energies of these transition states were in the order 52 < 53 < 54 < 55. Since the cyclization of 34a produced only 35a and 36a in an approximately 9:1 ratio via the respective transition states 52 and 53, these calculations correlated qualitatively with the experimental results.