Synthesis 2016; 48(11): 1684-1692
DOI: 10.1055/s-0035-1561432
special topic
© Georg Thieme Verlag Stuttgart · New York

Studies on the Second-Generation Approach to Loline Alkaloids: Synthesis of N-Bus-norloline through N-tert-Butanesulfinyl Imine Based Asymmetric Vinylogous Mannich Reaction

Jian-Liang Ye*
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. of China   Email: pqhuang@xmu.edu.cn   Email: yejl@xmu.edu.cn
,
Yang Liu
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. of China   Email: pqhuang@xmu.edu.cn   Email: yejl@xmu.edu.cn
,
Yu-Feng Zhang
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. of China   Email: pqhuang@xmu.edu.cn   Email: yejl@xmu.edu.cn
,
Zhi-Ping Yang
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. of China   Email: pqhuang@xmu.edu.cn   Email: yejl@xmu.edu.cn
,
Pei-Qiang Huang*
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. of China   Email: pqhuang@xmu.edu.cn   Email: yejl@xmu.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 16 February 2016

Accepted after revision: 17 March 2016

Publication Date:
13 April 2016 (eFirst)

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.

Supporting Information

 
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