Total Synthesis of Bipenicilisorin and Assignment of the Absolute Configuration

• Published in: Journal of natural products (Washington, D.C.) Vol. 87; no. 5; pp. 1394 - 1400
• Main Authors: Fukuda, Eigo, Fujiwara, Ibuki, Maruno, Shoki, Motomura, Kaiki, Endo, Seiya, Iwasaki, Arihiro, Fukuta, Tatsuya, Nakayama, Atsushi, Shinada, Tetsuro
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 24.05.2024; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; PHENOLS; DERIVATIVES; N-FORMYLSACCHARIN
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.4c00114

The first total synthesis of bipenicilisorin (1) isolated from Penicillium chrysogenum SCSIO 41001 via its monomer natural product, penicilisorin (2), was achieved. Penicilisorin was synthesized in four steps from a o-bromobenzaldehyde derivative via the Pd-catalyzed one-pot fluorocarbonylation/lactonization/β-elimination cascade reaction. Iodination of penicilisorin gave 7-iodopenicilisorin which was dimerized by Pd-catalyzed homodimerization to provide (±)-bipenicilisorin. The unknown absolute configuration of naturally occurring (+)-bipenicilisorin was examined by optical resolution of the (±)-synthetic bipenicilisorin and a comparison of experimental and theoretical electronic circular dichroism (ECD) spectra. These results support the absolute configuration of the natural product to be S a. A cytotoxic activity test of (+)-and (−)-bipenicilisorin using A549 cells revealed that (+)-1 has a lower IC50 value than (−)-1.