石川 勇人

Abstract Alstrostine A and isoalstrostine A are monoterpenoid indole alkaloid glycosides with unique structures found in the plant families Apocynaceae and Rubiaceae. With molecular weights exceeding 900, nine chiral centers (excluding sugar rings), and complex fused‐ring structures, the structural elucidation of these molecules using spectral analysis is highly challenging. Therefore, their structural identification through total synthesis is important in both natural product chemistry and synthetic organic chemistry. In this study, we successfully accomplished the first asymmetric total syntheses of these alkaloids in 18 or 19 steps. A key synthetic feature was a two‐ or three‐component coupling reaction between secologanin and a pyrrolidinoindoline moiety based on our proposed biosynthetic pathway. This approach enabled the synthesis of all isomers of the pyrrolidinoindoline ring, which constitutes the upper fragment of the alstrostines, and allowed us to revise the stereochemistry of alstrostine A. Additionally, a compound previously isolated as alstrostine A from Palicourea luxurians (Rubiaceae) was successfully reidentified and renamed as epialstrostine A.

There are many indole alkaloids that contain diverse functional groups attached to the benzene ring on the indole core. Promising biological activities of these alkaloids have been reported. Herein, we report the indole C5-selective bromination of indolo[2,3-a]quinolizidine alkaloids by adding nearly equimolar amounts of Br3·PyH and HCl in MeOH. The resulting reaction plausibly proceeds through an indoline intermediate by the nucleophilic addition of MeOH to the C3-brominated indolenine intermediate. Data support the intermediacy of a C3-, C5-dibrominated indolenine intermediate as a brominating agent. These conditions demonstrate excellent selectivity for indole C5 bromination of natural products and their derivatives. Thus, these simple, mild, and metal-free conditions allow for selective, late-stage bromination followed by further chemical modifications. The utility of the brominated product prepared from naturally occurring yohimbine was demonstrated through various derivatizations, including a bioinspired heterodimerization reaction.

The first enantioselective total synthesis of kopsiyunnanine B, which has a unique folded and complex pentacyclic structure containing six contiguous chiral centers, has been achieved along our originally proposed biosynthetic pathway. The key reaction of this synthesis includes a bioinspired cascade that builds three ring structures and three chiral centers in one step and features the stereoselective reduction of a β-acrylate and oxidation to an oxindole.