Studies on the Second-Generation Approach to Loline Alkaloids: Synthesis of N-Bus-norloline through N-tert-Butanesulfinyl Imine Based Asymmetric Vinylogous Mannich Reaction
Studies on the Second-Generation Approach to Loline Alkaloids: Synthesis of N-Bus-norloline through N-tert-Butanesulfinyl Imine Based Asymmetric Vinylogous Mannich Reaction
复制标题
黑麦草碱第二代合成途径研究：N-叔丁亚磺酰亚胺不对称乙烯基曼尼希反应合成N-Bus-正黑麦碱
DOI：
10.1055/s-0035-1561432
复制
发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Huang Pei-Qiang
中科院分区：
文献类型：
--
作者：
Ye Jian-Liang;Liu Yang;Zhang Yu-Feng;Yang Zhi-Ping;Huang Pei-Qiang
摘要综述了碱类生物碱的合成策略。这种第二代方法的特点是通过Cu(OTf)2介导的高反-非对对选择性的vinyous Mannich反应（VMR）与n - boc -2-叔丁基-（丁基二甲基硅氧基）吡罗（TBSOP）的Ellman n -叔丁基亚胺衍生的异丙基保护(S)-甘油醛（TBSOP）直接获得必需的邻近二氨基基基。采用弗莱明的方法在加合物的C4上引入羟基，得到了不需要的非对映体，收率为40%。在分子内用吡咯里啶衍生物SN反应建立醚桥是困难的，产率仅为20%。鉴于在这次调查中获得的有价值的信息，正在研究第二代方法的改进版本，该方法有望提供一种简明有效的方法来获得具有挑战性的洛碱生物碱。
Abstract A strategy is outlined for the synthesis of loline alkaloids. This second-generation approach features direct access to the requisite vicinal diamino motif by a Cu(OTf)2-mediated highly trans-diastereoselective vinylogous Mannich reaction (VMR) of Ellman N-tert-butanesulfinyl imine derived from isopropylidene-protected (S)-glyceraldehyde, with N-Boc-2-tert-(butyldimethylsilyloxy)pyrrole (TBSOP). Fleming’s method was employed for the introduction of a hydroxyl group at C4 of the adduct, which gave the undesired diastereomer in 40% yield. The intramolecular SN reaction of the pyrrolizidine derivative to build the etheral bridge proved to be difficult, and produced N-Bus-norloline in only 20% yield. In light of the valuable information gained during this investigation, an improved version of the second-generation approach is being investigated, which is expected to provide a concise and efficient access to the challenging loline alkaloids.