Concise Total Synthesis of Tronocarpine

• Published in: Angewandte Chemie International Edition Vol. 60; no. 2; pp. 635 - 639
• Main Authors: Nakayama, Atsushi, Nakamura, Tenta, Zaima, Toshihiro, Fujimoto, Saho, Karanjit, Sangita, Namba, Kosuke
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 11.01.2021; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Aldehydes; Alkaloids; Chemistry; Chemistry, Multidisciplinary; equilibrium; Functional groups; Indoles; natural products; Physical Sciences; Science & Technology; Synthesis; tandem cyclization; total synthesis; IBOGAN; alkaloids; BISINDOLE ALKALOIDS; REVERSAL; TABERNAEMONTANA; natural products; tandem cyclization; RING; A-D; RESISTANCE; equilibrium; total synthesis; INDOLE ALKALOIDS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202009966

A concise total synthesis of tronocarpine, a chippiine‐type indole alkaloid, was accomplished. The key feature of this total synthesis is a one‐pot construction of the pentacyclic skeleton containing an azabicyclo[3.3.1]nonane core by tandem cyclization from an indole derivative with all carbon side chains and functional groups. This tandem cyclization consists of α,β‐unsaturated aldehyde formation, intramolecular aldol reaction, six‐membered lactamization, azide reduction, and seven‐membered lactamization. The stereochemical outcome in this tandem cyclization is controlled by the stereocenter at the C14 position. This strategy can be utilized to synthesize other chippiine‐type alkaloids with azabicyclo[3.3.1]nonane skeletons. A concise total synthesis of a chippiine‐type alkaloid, tronocarpine, was accomplished. The key feature of this total synthesis was construction of the key pentacyclic skeleton with an azabicyclo[3.3.1]nonane core, which required a one‐pot process including i) β‐elimination, ii) intramolecular aldol reaction, iii) six‐membered lactamization, iv) azide reduction, and v) seven‐membered lactamization.