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Stereoselective total synthesis of lupin alkaloids

Stereoselective total synthesis of lupin alkaloids
Stereoselective total synthesis of lupin alkaloids
A highly anti-selective formal imino-aldol methodology has been developed and applied to asymmetric total synthesis of five alkaloids, including (+)-lupinine, ()-epitashiromine, (–)-epilamprolobine, (+)-isosophoridine and (+)-sparteine. This method combined an imino-aldol reaction and anti-alkylation, with a variety of (S)-p-tolylsulfinimines, to give anti-products with high diastereoselectivity (dr >10:1). Absolute stereochemical determination of the anti-product was proved by the synthesis of (+)-lupinine and ()-epitashiromine in 17% and 23% overall yields respectively.
The first total synthesis of the tetracyclic lupin alkaloid (+)-isosophoridine has been completed in 10 steps in 9% overall yield. The target molecule was assembled with excellent control of contiguous stereocenters employing an anti-selective formal imino-aldol reaction and N-acyliminium cyclisation as key steps. As a part of our studies towards (+)-isosophoridine, we performed the first total synthesis of the tricyclic alkaloid (–)-epilamprolobine.
In addition, based on the anti-selective methodology and good understanding of N-acyliminium cyclisation chemistry, a total synthesis of (+)-sparteine has been achieved in 16 linear steps and 1.6% overall yield, which employed a cross metathesis to assemble the allyl silane present in the N-acyliminium precursor.
University of Southampton
Lyu, Xiang
7f7ef8c1-9d89-440d-9ff5-c4be0482a4e8
Lyu, Xiang
7f7ef8c1-9d89-440d-9ff5-c4be0482a4e8
Brown, Richard C.D.
21ce697a-7c3a-480e-919f-429a3d8550f5

Lyu, Xiang (2018) Stereoselective total synthesis of lupin alkaloids. University of Southampton, Doctoral Thesis, 195pp.

Record type: Thesis (Doctoral)

Abstract

A highly anti-selective formal imino-aldol methodology has been developed and applied to asymmetric total synthesis of five alkaloids, including (+)-lupinine, ()-epitashiromine, (–)-epilamprolobine, (+)-isosophoridine and (+)-sparteine. This method combined an imino-aldol reaction and anti-alkylation, with a variety of (S)-p-tolylsulfinimines, to give anti-products with high diastereoselectivity (dr >10:1). Absolute stereochemical determination of the anti-product was proved by the synthesis of (+)-lupinine and ()-epitashiromine in 17% and 23% overall yields respectively.
The first total synthesis of the tetracyclic lupin alkaloid (+)-isosophoridine has been completed in 10 steps in 9% overall yield. The target molecule was assembled with excellent control of contiguous stereocenters employing an anti-selective formal imino-aldol reaction and N-acyliminium cyclisation as key steps. As a part of our studies towards (+)-isosophoridine, we performed the first total synthesis of the tricyclic alkaloid (–)-epilamprolobine.
In addition, based on the anti-selective methodology and good understanding of N-acyliminium cyclisation chemistry, a total synthesis of (+)-sparteine has been achieved in 16 linear steps and 1.6% overall yield, which employed a cross metathesis to assemble the allyl silane present in the N-acyliminium precursor.

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Xiang Lyu Thesis - Version of Record
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Published date: September 2018

Identifiers

Local EPrints ID: 429608
URI: http://eprints.soton.ac.uk/id/eprint/429608
PURE UUID: 19800bbd-afbd-4ae7-929b-75f399f34dec
ORCID for Richard C.D. Brown: ORCID iD orcid.org/0000-0003-0156-7087

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Date deposited: 01 Apr 2019 16:30
Last modified: 30 Jan 2020 05:06

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Contributors

Author: Xiang Lyu
Thesis advisor: Richard C.D. Brown ORCID iD

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