Recent progress in the total synthesis of calyciphylline A-type Daphniphyllum alkaloid himalensine A Calyciphylline A-型虎皮楠生物碱himalensine A的全合成研究进展

Hu，Jingping1,2,3; Chen，Yuye2,3; Xu，Jing2,3

2021-09-01

10.1360/TB-2021-0018

Chinese Science Bulletin-Chinese   影响因子和分区

0023-074X

2095-9419

The evergreen plants of the genus Daphniphyllum are found mainly in the Asia-Pacific region and have played important roles in Traditional Chinese Medicine. Their leaves, barks and fruits have long been used to treat a variety of ailments including asthma, rheumatism, inflammation and fever. Since the isolation of daphnimacrine by the Yagi group in 1909, more than 330 structurally fascinating natural products, known as the Daphniphyllum alkaloids, have been isolated and structurally identified over the years. Owing to their unusual and disparate structural backbones, these alkaloids are highly attractive to synthetic chemists, spanning all around the world. Based on their distinct skeletons, these natural compounds can be categorized into 13-35 subfamilies. Among which, calyciphylline A-type is a particularly notable major subfamily that consists of approximately 20 members. These alkaloids show extensive physiological activities, such as anti-HIV and cytotoxicity and so on. Calyciphylline A-type alkaloids possess a characteristic structural backbone consisting of four fused rings [6-6-5-7] with one or more quaternary stereocenters. In 2016, a unique member of this family, namely himalensine A, was isolated from Nepalese Daphniphyllum himalense by Yue group. While its bioactivity remains unexplored, himalensine A possesses an unprecedented skeleton in the calyciphylline A-type alkaloids, which is the first natural C19 Daphniphyllum alkaloid isolated so far. Congested pentacyclic ring skeleton that includes a unique 2-azabicyclo[3.3.1]nonane motif, six stereogenic centers, and an all-carbon quaternary center, makes himalensine A a formidable synthetic challenge. Since its isolation, three impressive total syntheses of himalensine A have been reported by Dixon, Xu and Gao groups, respectively. In 2017, the first enantioselective total synthesis of (-)-himalensine A was disclosed by Dixon and his co-workers. The total synthesis was elegantly accomplished in 22 linear steps. Enantioselective prototropic shift/furan Diels-Alder (IMDAF) cascade reaction to construct the ACD tricycle system and a reductive radical cyclization to build the B ring are notable highlights of Dixon's synthesis. Other notable highlights include a molecular oxygen mediated γ-CH oxidation and a Stetter cyclization to access the critical cyclopentenone ring to achieve the full core of the natural product. Finally, a highly chemoselective lactam reduction delivered the target natural product. In 2019, Xu and co-workers accomplished an efficient total synthesis of (-)-himalensine A in 14 steps. Key features of this strategy include a Cu-catalyzed nitrile hydration and Michael addition to construct C ring, a Heck reaction to construct the challenging 2-azabicyclo[3.3.1]nonane motif, and a Meinwald rearrangement reaction to deliver the necessary carbonyl group, which significantly improved the overall synthetic efficiency. Concurrently, Gao and his co-workers reported the total synthesis of himalensine A in a new fashion. They developed a 1,3-dipolar nitrone [3+2] cycloaddition reaction to construct A ring. The Pd-catalyzed enolate alkenylation was employed to fabricate B ring, followed by the construction of the seven-membered ring via a ring closing metathesis reaction. Finally, a Lewis acid-promoted Nazarov cyclization successfully furnished the cyclopentanone F ring. Besides these total synthetic approaches, several other interesting synthetic studies along with noteworthy synthetic strategies reported by the Bonjoch, Stockdill and Hudlicky groups, have showcased valuable and pioneering strategies and methods for the synthesis of himalensine A and its related Daphniphyllum alkaloids. This review covers the efforts toward the synthesis of himalensine A spanning the period from 2017 to 2020. The innovative strategies and methods demonstrated in these impressive efforts are inspiring to the synthesis of various types of Daphniphyllum alkaloids and many other natural products.

Calyciphylline A Daphniphyllum alkaloids Himalensine A Natural product total synthesis

EI

中文

通讯

20213910941917

Diseases ; Enantioselectivity ; Musculoskeletal system ; Plants (botany) ; Synthesis (chemical)

Biomechanics, Bionics and Biomimetics:461.3 ; Physical Chemistry:801.4 ; Chemical Reactions:802.2 ; Chemical Products Generally:804

2-s2.0-85115442179

Scopus

1.School of Chemistry and Chemical Engineering,Harbin Institute of Technology,Harbin,150001,China
2.Department of Chemistry and Shenzhen Grubbs Institute,Southern University of Science and Technology,Shenzhen,518055,China
3.Guangdong Provincial Key Laboratory of Catalysis,Shenzhen,518055,China

Hu，Jingping,Chen，Yuye,Xu，Jing. Recent progress in the total synthesis of calyciphylline A-type Daphniphyllum alkaloid himalensine A Calyciphylline A-型虎皮楠生物碱himalensine A的全合成研究进展[J]. Chinese Science Bulletin-Chinese,2021,66(25):3241-3250.

Hu，Jingping,Chen，Yuye,&Xu，Jing.(2021).Recent progress in the total synthesis of calyciphylline A-type Daphniphyllum alkaloid himalensine A Calyciphylline A-型虎皮楠生物碱himalensine A的全合成研究进展.Chinese Science Bulletin-Chinese,66(25),3241-3250.

Hu，Jingping,et al."Recent progress in the total synthesis of calyciphylline A-type Daphniphyllum alkaloid himalensine A Calyciphylline A-型虎皮楠生物碱himalensine A的全合成研究进展".Chinese Science Bulletin-Chinese 66.25(2021):3241-3250.