Synthesis and Structural Confirmation of the Thiazole Alkaloids Derived from Peganum harmala L.

Myeonghyeon Sim,Youngtaek Han,Sujin Lee

doi:10.3390/app12010078

Myeonghyeon Sim, Youngtaek Han + Show 1 more

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https://doi.org/10.3390/app12010078

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Abstract

Peganumal A and B are thiazole alkaloids isolated from the seeds of Peganum harmala L. Thiazole moieties are rarely found in natural products, but diverse compounds possessing thiazole moieties have attracted attention owing to their broad range of biological activities. Peganumals are the first natural thiazole compounds isolated from the genus Peganum. It was difficult to define the exact structure of peganumal A via spectroscopic analysis. In this paper, we report the first total synthesis of peganumal A and B. The 5-benzylthiazole skeleton possessing methyl or hydrogen at the 2-position of the peganumals was efficiently constructed via the Hantzsch thiazole synthesis of the α-bromoaldehyde intermediate. Moreover, the spectral data of the synthetic 2H–thiazole compound were identical to those previously reported for peganumal A. The synthesis allowed the confirmation of the structure of peganumal A.

Highlights

Peganum harmala L. (Zygophyllaceae), known as the Syrian rue, is an abundant wildgrowing flowering plant
2-position of the peganumals was efficiently constructed via the Hantzsch thiazole synthesis of the α-bromoaldehyde intermediate
It was claimed that thiazole was a rarely observed moiety in natural products and was reported for the first time in the genus Peganum [4]

Summary

Introduction

Peganum harmala L. (Zygophyllaceae), known as the Syrian rue, is an abundant wildgrowing flowering plant. A Chinese research group isolated the natural thiazole alkaloids peganumal A (1) and B (2) from the seeds of Peganum harmala L. They evaluated their antiproliferative activities against HL-60, PC-3, and SGC-7901 cancer cell lines, but 1 and 2 did not show significant activities. It was claimed that thiazole was a rarely observed moiety in natural products and was reported for the first time in the genus Peganum [4]. They proposed that 1 and 2 have 2H–thiazole or 2-methylthiazole moieties connected with 4-hydroxy3,5-dimethoxybenzene by a methylene bridge, respectively (Figure 1). Unlike 2, it was difficult to distinguish 1 by two-dimensional NMR studies from its possible regioisomer

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