Synthesis of Ganbajunins D and E and the Proposed Structure of Thelephantin D

• Published in: European journal of organic chemistry 2015-09, Vol.2015 (26), p.5798-5809
• Main Authors: Fujiwara, Kenshu, Kushibe, Keisuke, Sato, Takuto, Norikura, Toshio, Matsue, Hajime, Iwai, Kunihisa, Katoono, Ryo, Suzuki, Takanori
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Natural products; NMR; Nuclear magnetic resonance; Structure elucidation; Total synthesis; Transesterification
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201500722

The syntheses of ganbajunins D and E and of the structure proposed for thelephantin D, as well as its regioisomer, were achieved in a divergent manner via a common monoester intermediate. The proposed structure of thelephantin D had NMR chemical shifts different from those of natural thelephantin D. This supported Takahashi's suggestion that the true structure of natural thelephantin D should be the same as that of terrestrin C, as was deduced from the similarities in their NMR spectra. The presence of isomerization equilibria between 2′,5′‐ and 2′,6′‐diacyloxy‐p‐terphenyl derivatives in solution, which are the cause of the inseparability of these derivatives, was also demonstrated by monitoring the dynamic transition from a 2′,6′‐diacyloxy‐p‐terphenyl‐rich mixture of the derivatives to an equilibrium mixture. The results of biological and chemical property tests – such as cytotoxicity against cancer cells, affinity towards Fe2+ ion, and antioxidative activity – with the synthesized compounds are also described. The syntheses of the 2′,5′‐ and 2′,6′‐diacyloxy‐p‐terphenyl compounds ganbajunins D and E and of the structure proposed for thelephantin D, as well as its regioisomer, were achieved in a divergent manner via a common monoester intermediate. The proposed structure of thelephantin D was, however, found to be different from that of natural thelephantin D on the basis of NMR chemical shifts.