Protecting-Group-Free Total Synthesis of (-)-Jiadifenolide: Development of a [4 + 1] Annulation toward Multisubstituted Tetrahydrofurans.

Abstract

A concise, protecting-group-free total synthesis of (-)-jiadifenolide, a synthetically challenging seco-prezizaane sesquiterpene with potent neurotrophic activity, is reported. The convergent route features a SmI2/H2O-mediated stereoselective reductive cyclization, an unprecedented formal [4 + 1] annulative tetrahydrofuran-forming reaction and programmed redox manipulations. The newly developed annulation of β-hydroxy aldehydes or ketones with lithium trimethylsilyldiazomethane provides access to a diverse array of multisubstituted tetrahydrofurans. The synthetic jiadifenolide exhibited weak cytotoxicity against five human cancer cell lines.

• Authors: Yang Shen, Linbin Li, Zhisheng Pan, Yinglu Wang, Jundong Li, Kuangyu Wang, Xiance Wang, Youyu Zhang, Tianhui Hu, Yandong Zhang
• Journal: Organic letters (Org Lett) Vol. 17 Issue 21 Pg. 5480-3 (Nov 06 2015) ISSN: 1523-7052 [Electronic] United States
• PMID: 26509873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aldehydes
• Antineoplastic Agents
• Furans
• Sesquiterpenes
• jiadifenolide

Topics

• Aldehydes
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cyclization
• Furans (chemistry)
• Illicium (chemistry)
• Molecular Structure
• Oxidation-Reduction
• Sesquiterpenes (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism