Site-selective C-H hydroxylation of pentacyclic triterpenoids directed by transient chiral pyridine-imino groups

• Published in: Nature communications Vol. 11; no. 1; p. 4371
• Main Authors: Mu, Tong, Wei, Bingcheng, Zhu, Dapeng, Yu, Biao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/935; 639/638/403/977; 639/638/549/933; Accessibility; Chirality; Humanities and Social Sciences; Hydroxyl groups; Hydroxylation; multidisciplinary; Natural products; Oxidation; Pentacyclic triterpenoids; Pyridines; Saponins; Science; Science (multidisciplinary); Synthesis; Triterpenoids; Valence
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18138-9

Pentacyclic triterpenoids (PTs) constitute one of the biggest families of natural products, many with higher oxidation state at the D/E rings possess a wide spectrum of biological activties but are poorly accessible. Here we report a site-selective C-H hydroxylation at the D/E rings of PTs paving a way toward these important natural products. We find that Schönecker and Baran’s Cu-mediated aerobic oxidation can be applied and become site-selective on PT skeletons, as being effected unexpectedly by the chirality of the transient pyridine-imino directing groups. To prove the applicability, starting from the most abundant triterpenoid feedstock oleanane, three representative saponins bearing hydroxyl groups at C16 or C22 are expeditiously synthesized, and barringtogenol C which bears hydroxyl groups at C16, C21, and C22 is synthesized via a sequential hydroxylation as the key steps. Pentacyclic triterpenoids (PTs) functionalized at the D/E rings possess a wide spectrum of biological activities but are poorly accessible. Here, the authors report a site-selective C-H hydroxylation at the D/E rings of PTs by exploiting transient pyridine-imino directing groups and disclose the synthesis of related natural products.