Total Synthesis of (+)‐3‐Deoxyfortalpinoid F, (+)‐Fortalpinoid A, and (+)‐Cephinoid H

Abstract

3‐Deoxyfortalpinoid F, fortalpinoid A, and cephinoid H are members of the Cephalotaxus diterpenoids class of natural products, which feature diverse chemical structures and valuable biological activities. We report herein the development of a diastereoselective Pauson–Khand reaction as an effective pathway to access the core tetracyclic skeleton, which is found widely in Cephalotaxus diterpenoids. Furthermore, we enabled the construction of the tropone moiety through a ring‐closing metathesis/elimination protocol. Based on the developed strategy, asymmetric synthesis of the title compounds has been achieved for the first time.

Construction of Tetracyclic Core Skeleton of Cephalotaxus Diterpenoids through Diastereoselective Pauson‐Khand Reaction

“… Asymmetric Construction of Tetracyclic Core Skeleton and Synthesis of (+)‐3‐Deoxyfortalpinoid F, (+)‐Fortalpinoid A, and (+)‐Cephinoid H [14] …”

“…We successfully established a reliable pathway to this tetracyclic core skeleton based on a diastereoselective Pauson‐Khand reaction strategy. As a result, the first asymmetric total synthesis of (+)‐3‐deoxyfortalpinoid F, (+)‐fortalpinoid A, and (+)‐cephinoid H had been achieved [14] . Herein, we report the detail on the development of the diastereoselective Pauson‐Khand reaction, which affords an effective mean to the tetracyclic core skeleton.…”

“…As a result, the first asymmetric total synthesis of (+)-3-deoxyfortalpinoid F, (+)-fortalpinoid A, and (+)-cephinoid H had been achieved. [14] Herein, we report the detail on the development of the diastereoselective Pauson-Khand reaction, which affords an effective mean to the tetracyclic core skeleton.…”

Stereoselective Synthesis of (±)-Cephanolide B

“…The interesting frameworks and bioactivity of cephanolides have inspired many creative and informative total syntheses. This has culminated in the total syntheses of 1 – 6 since 2018, including (i) the total synthesis of (±)-cephanolides B ( 2 ) and C ( 3 ) via an innovative Pd-catalyzed carbonylative Heck cascade reaction as a key step, reported by Zhao and co-workers in 2018 (Figure a); (ii) an asymmetric synthesis of cephanolide A ( 1 ) and B ( 2 ) via a Prins-type cyclization as a key step, reported by Gao and co-workers in 2020 (Scheme b); (iii) the total synthesis of cephanolides A–D ( 1 – 4 ) using an intramolecular inverse-demand Diels–Alder cycloaddition, reported by Sarpong and co-workers (Figure c); and (iv) the total synthesis of fortalpinoid A and cephinoid H ( 5 , 6 ) using an intramolecular Pauson-Khand (PK) reaction, reported by Hu and co-workers (Figure d) …”

“…We envisaged that increasing the steric hindrance of the bottom face might lead to the Co 2 (CO) 8 complex approaching the top face of enyne motif of 27 (Scheme ) to afford the desired product 28 predominantly. To explore the synthetic feasibility, lactone 9 was first reduced with DIBAL-H in DCM at −78 °C to afford aldehyde 25 in 64% yield.…”