Stephen Michael Rajesh, Rahman M Toufiqur, Tiruveedhula V V N Phani Babu, Fonseca German O, Deschamps Jeffrey R, Cook James M
Department of Chemistry & Biochemistry, University of Wisconsin-Milwaukee, 3210 North Cramer Street, Milwaukee, Wisconsin, 53211, USA.
Center for Biomolecular Science and Engineering, Naval Research Laboratory, Code 6930, Washington, DC, 20375, USA.
Chemistry. 2017 Nov 7;23(62):15805-15819. doi: 10.1002/chem.201703572. Epub 2017 Oct 18.
A highly enantio- and diastereoselective strategy to access any member of the sarpagine/macroline family of oxindole alkaloids via internal asymmetric induction was developed from readily available d-(+)-tryptophan. At the center of this approach was the diastereospecific generation of the spiro[pyrrolidine-3,3'-oxindole] moiety at an early stage via a tert-butyl hypochlorite-promoted oxidative rearrangement of a chiral tetrahydro-β-carboline derivative. This key branching point determined the spatial configuration at the C-7 spiro center to be entirely 7R or 7S. Other key stereospecific processes were the asymmetric Pictet-Spengler reaction and Dieckmann cyclization, which were scalable to the 600 and 150 gram levels, respectively. Execution of this approach resulted in first enantiospecific total synthesis of (+)-isoalstonisine and (-)-macrogentine from the chitosenine series (7R), as well as (+)-alstonisine, (+)-alstofoline, (-)-alstonoxine A and (+)-N -demethylalstonisine from the alstonisine series (7S).
从易得的d-(+)-色氨酸出发，开发了一种通过分子内不对称诱导获得任何色胺酮/大麦芽碱类氧化吲哚生物碱家族成员的高度对映体和非对映体选择性策略。该方法的核心是在手性四氢-β-咔啉衍生物的叔丁基次氯酸盐促进的氧化重排作用下，在早期阶段非对映体特异性地生成螺[吡咯烷-3,3'-氧化吲哚]部分。这个关键分支点决定了C-7螺中心的空间构型完全为7R或7S。其他关键的立体特异性过程是不对称Pictet-Spengler反应和Dieckmann环化反应，它们分别可扩大到600克和150克规模。实施该方法首次实现了从壳杉宁系列（7R）对映体特异性全合成(+)-异阿尔斯顿宁和(-)-大麦芽碱，以及从阿尔斯顿宁系列（7S）全合成(+)-阿尔斯顿宁、(+)-阿尔斯托弗林、(-)-阿尔斯顿诺辛A和(+)-N-去甲基阿尔斯顿宁。
