Article

Total synthesis of (+)-perophoramidine and determination of the absolute configuration.

Department of Medicinal Natural Products and Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
Journal of the American Chemical Society (impact factor: 9.91). 10/2010; 132(40):14052-4. DOI:10.1021/ja1070043 pp.14052-4
Source: PubMed

ABSTRACT The first asymmetric total synthesis of (+)-perophoramidine has been achieved in 17 steps with ∼11% overall yield. The key step relies on an asymmetric biomimetic Diels-Alder reaction between the in situ-generated chiral diene T-24 and the substituted tryptamine 23 to assemble the core structure 27a in a highly efficient way. An acid-catalyzed thermodynamic equilibrium results in C═N double-bond migration of the amidine moiety in 37, which guarantees a regioselective methylation on N(1) at the end of the synthesis. The absolute configuration of (+)-perophoramidine was determined by X-ray crystallographic analysis of the chiral intermediate 32 and comparison of the rotation of synthetic (+)-perophoramidine with that of the natural product.

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Keywords

amidine moiety
 
asymmetric biomimetic Diels-Alder reaction
 
chiral intermediate 32
 
core structure 27a
 
C═N double-bond migration
 
efficient way
 
first asymmetric total synthesis
 
natural product
 
regioselective methylation
 
situ-generated chiral diene T-24