Stereodivergent total synthesis of chlorofusin and its all seven chromophore diastereomers

• Published in: Tetrahedron Vol. 71; no. 2; pp. 370 - 380
• Main Authors: Qiu, Hai-Bo, Qian, Wen-Jian, Yu, Shun-Ming, Yao, Zhu-Jun
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 14.01.2015; Elsevier
• Subjects: Azaphilone; Chemistry; Chemistry, Organic; Chlorofusin; Chromophores; Economics; Hydrocarbons; Linkages; p53-MDM2 interaction; Physical Sciences; Precursors; Science & Technology; Stereodivergent synthesis; Synthesis (chemistry); Tetrahedrons; Total synthesis; p53-MDM2 interaction; Chlorofusin; Azaphilone; Total synthesis; Stereodivergent synthesis; P53-HDM2 INTERACTION; OXIDATIVE DEAROMATIZATION; OLEFIN-METATHESIS CATALYSTS; SOLID-PHASE SYNTHESIS; P53 PROTEIN; CYCLIC PEPTIDE PORTION; P53/MDM2 INTERACTION; MDM2; INHIBITOR
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2014.10.062

Chlorofusin (1), one of few natural antagonists against p53-MDM2 interactions, is a naturally biogenetic hybrid composed of a 27-membered nonacyclopeptide and a unique chromophore through the hydrocarbon linkage with ornithine. In this article, we describe our recent achievement, in details, of developing a convenient stereodivergent route for parallel total synthesis of chlorofusin (1) and its all seven chromophore diastereomers (1a–1g) in enantiopure forms, starting from a common racemic azaphilone precursor 10. The newly developed total synthesis shows the great advantages of economy, scalability, stable intermediates, high yields, ease of HPLC-free operations and reduplication. [Display omitted]