Asymmetric Total Synthesis of (-)-Swainsonine from Inexpensive and Commercially Available Starting Material, Ascorbic Acid
Zheng Yang Lee,1, a) Jhi Biau Foo,1, 2, b) Mohd Fazli Mohammat,3, c) and Agustono Wibowo4, d)

1) School of Pharmacy, Faculty of Health & Medical Sciences, Taylor^s University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
2) Centre for Drug Discovery and Molecular Pharmacology, Faculty of Health & Medical Sciences, Taylor^s University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
3) Organic Synthesis Laboratory, Institute of Science, University Teknologi MARA (UiTM), 40450, Shah Alam, Selangor, Malaysia
4) Faculty of Applied Science, University Teknologi MARA (UiTM) Pahang, Jengka Campus, 26400, Bandar Tun Abdul Razak Jengka, Pahang, Malaysia

Abstract

Swainsonine is a natural and synthetic alpha-mannosidase II inhibitor which has been shown to inhibit various types of cancer growth in vitro and in vivo. In this study, a practical stereoselective total synthesis of (-)-swainsonine has been achieved by using inexpensive, commercially available D-isoascorbic acid. This pivotal route relies upon several protection and deprotection steps, Swern Oxidation, Horner-Wadsworth-Emmons reaction and intramolecular 1,3 dipolar cycloaddition. The challenges associated with existence of aldehyde-lactol tautomerism were also highlighted in this work.

Keywords: swainsonine, lactol tautomerism, HWE reaction, selective acetylation

Topic: Organic Chemistry