Protecting-Group-Free Total Synthesis of (-)-Jiadifenolide: Development of a [4 + 1] Annulation toward Multisubstituted Tetrahydrofurans.
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.
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, China.
Yang
Y
Shen
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, China.
Linbin
L
Li
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, China.
Zhisheng
Z
Pan
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, China.
Yinglu
Y
Wang
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, China.
Jundong
J
Li
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, China.
Kuangyu
K
Wang
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, China.
Xiance
X
Wang
Cancer Research Center, Xiamen University Medical College , Xiamen, Fujian 361005, China.
Youyu
Y
Zhang
Cancer Research Center, Xiamen University Medical College , Xiamen, Fujian 361005, China.
Tianhui
T
Hu
Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, China.
Yandong
Y
Zhang
D000447:Aldehydes; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D005663:Furans / Q000737:chemistry*; D029523:Illicium / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D000447:Aldehydes; D000970:Antineoplastic Agents; D005663:Furans; D012717:Sesquiterpenes; C546282:jiadifenolide