Dedicated to Professor Cesare Gennari on the occasion of his 65^th birthday

Abstract

The assignment of two stereocenters of the natural product haprolid through the application of a profile hidden Markov model (HMM) and its confirmation through total synthesis of the natural product and of two of its diastereomers are reported. The structure elucidation of this polyketide-peptide hybrid natural product is a telling showcase of how difficult it can be to determine the absolute configuration of isolated stereocenters and the benefits of a gene cluster analysis for structure determination. The key steps of the synthesis are a selective epoxidation of a terminal olefin and the stereodivergent macrolactonization strategy. Furthermore, the biological evaluation of all products showed that all diastereomers are potent inhibitors of hepatocellular carcinoma cell lines.

The assignment of two stereocenters of the natural product haprolid through the application of a profile hidden Markov model (HMM) and its confirmation through total synthesis of the natural product and of two of its diastereomers are reported. The structure elucidation of this polyketide-peptide hybrid natural product is a telling showcase of how difficult it can be to determine the absolute configuration of isolated stereocenters and the benefits of a gene cluster analysis for structure determination. The key steps of the synthesis are a selective epoxidation of a terminal olefin and the stereodivergent macrolactonization strategy. Furthermore, the biological evaluation of all products showed that all diastereomers are potent inhibitors of hepatocellular carcinoma cell lines.

中文翻译：

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哈普利德的结构解析

专用于塞萨尔·根纳里教授在他的65之际^个生日

抽象的

据报道，通过应用隐型马尔可夫模型（HMM）分配了天然产物卤虫酯的两个立构中心，并通过完全合成天然产物及其两个非对映异构体对其进行了确认。该聚酮肽-多肽杂合天然产物的结构阐明清楚地表明了确定孤立的立体中心的绝对构型有多困难，以及基因簇分析对结构确定的好处。合成的关键步骤是末端烯烃的选择性环氧化和立体发散大内酯化策略。此外，所有产品的生物学评估表明，所有非对映异构体都是肝细胞癌细胞系的有效抑制剂。

据报道，通过应用隐型马尔可夫模型（HMM）分配了天然产物卤虫酯的两个立构中心，并通过完全合成天然产物及其两个非对映异构体对其进行了确认。该聚酮肽-多肽杂合天然产物的结构阐明清楚地表明了确定孤立的立体中心的绝对构型有多困难，以及基因簇分析对结构确定的好处。合成的关键步骤是末端烯烃的选择性环氧化和立体发散大内酯化策略。此外，所有产品的生物学评估表明，所有非对映异构体都是肝细胞癌细胞系的有效抑制剂。