Carroll Anthony W, Pyne Stephen G
School of Chemistry, University of Wollongong, Wollongong, New South Wales, Wollongong NSW 2522, Australia.
Curr Org Synth. 2019;16(4):498-522. doi: 10.2174/1570179416666190126100312.
The inherent glycosidase inhibitory activity and potentially therapeutic value of the polyhydroxylated pyrrolizidine alkaloids containing a hydroxymethyl substituent at the C-3 position have been well documented. Belonging to this class, the naturally occurring hyacinthacine C-type alkaloids are of general interest among iminosugar researchers. Their selective micromolar α -glycosidase inhibitory ranges (10 - 100 μM) suggest that these azasugars are potential leads for treating type II diabetes. However, the structures of hyacinthacine C1, C3 and C4 are insecure with hyacinthacine C5 being recently corrected.
This review presents the hyacinthacine C-type alkaloids: their first discovery to the most recent advancements on the structures, biological activities and total synthesis.
The hyacinthacine C-type alkaloids are of exponentially increasing interest and will undoubtedly continue to be reported as synthetic targets. They represent a challenging but rewarding synthetic feat for the community of those interested in accessing biologically active iminosugars. Since 2009, ten total syntheses have been employed towards accessing similarly related products but only three have assessed the glycosidase inhibitory activity of the final products. This suggests the need for an accessible and universal glycosidase inhibitory assay so to accurately determine the structure-activity relationship of how the hyacinthacine C-type alkaloids inhibit specific glycosidases. Confirming the correct structures of the hyacinthacine C-type alkaloids as well as accessing various analogues continues to strengthen the foundation towards a marketable treatment for type II diabetes and other glycosidase related illnesses.
在C-3位含有羟甲基取代基的多羟基吡咯里西啶生物碱的固有糖苷酶抑制活性和潜在治疗价值已有充分记录。属于这一类别的天然存在的海葱碱C型生物碱在亚氨基糖研究人员中受到广泛关注。它们选择性的微摩尔级α-糖苷酶抑制范围（10 - 100μM）表明这些氮杂糖是治疗II型糖尿病的潜在先导化合物。然而，海葱碱C1、C3和C4的结构并不确定，而海葱碱C5的结构最近已得到修正。
本综述介绍了海葱碱C型生物碱：从它们的首次发现到结构、生物活性和全合成方面的最新进展。
海葱碱C型生物碱的关注度呈指数级增长，无疑将继续作为合成目标被报道。对于那些对获取具有生物活性的亚氨基糖感兴趣的群体来说，它们代表了一项具有挑战性但回报丰厚的合成壮举。自2009年以来，已经进行了十次全合成以获取类似相关产品，但只有三次评估了最终产品的糖苷酶抑制活性。这表明需要一种可及的通用糖苷酶抑制测定方法，以便准确确定海葱碱C型生物碱抑制特定糖苷酶的构效关系。确认海葱碱C型生物碱的正确结构以及获取各种类似物继续加强了针对II型糖尿病和其他与糖苷酶相关疾病的适销对路治疗方法的基础。
