Literature Report 2. Total Synthesis of Longeracinphyllin A and (-)-Calyciphylline N. Date :

Transcription

1 Literature Report 2 Total Synthesis of Longeracinphyllin A and (-)-Calyciphylline N Reporter : Kui Liu Checker : Shao-Jie Cheng Date : Ang Li. et al. J. Am. Chem. Soc. 2017, 139, Amos B. Smith, III. et al. J. Am. Chem. Soc. 2014, 136,

2 Contents 1 Introduction 2 Total Synthesis of Longeracinphyllin A 3 Total Synthesis of (-)-Calyciphylline N (1) 4 Summary 2

3 CV of Prof. Ang Li Background: B.Sc., Peking University Ph.D., The Scripps Research Institute Research fellow., Institute of Chemical and Engineering Sciences 2010-Now Prof., Shanghai Institute of Organic Chemistry Research Interests: Total synthesis of structually and biologically interesting natural products 3

4 Introduction of Daphniphyllum Alkaloids Ang Li. et al. J. Am. Chem. Soc. 2017, 139,

5 Introduction of Longeracinphyllin A Longeracinphyllin A was isolated by Hao and co-workers from the leaves of Daphniphyllum longeracemosum; Its six consecutive stereocenters including the vicinal quaternary centers pose a challenge for chemical synthesis. Ang Li. et al. J. Am. Chem. Soc. 2017, 139,

6 Mitsunobu Reaction 6

7 Horner-Wadsworth-Emmons olefination 7

8 Retrosynthetic Analysis of Longeracinphyllin A 8

9 Retrosynthetic Analysis of Longeracinphyllin A 9

10 Completion of the Synthesis of Longeracinphyllin A 10

11 Completion of the Synthesis of Longeracinphyllin A 11

12 Completion of the Synthesis of Longeracinphyllin A 12

13 Completion of the Synthesis of Longeracinphyllin A 13

14 Completion of the Synthesis of Longeracinphyllin A 14

15 Introduction of (-)-Calyciphylline N Calyciphylline N was isolated in 2008 by Kobayashi and co-workers; Calyciphylline N include six contiguous stereogenic centers, three of which are quaternary bridgehead, a fused A ring dihydropyrrole. Amos B. Smith, III. et al. J. Am. Chem. Soc. 2014, 136,

16 Birch Reduction 16

17 Stille Carbonylative Cross-Coupling 17

18 Tsuji-Trost Allylation 18

19 Retrosynthetic Analysis of (-)-Calyciphylline N (1) 19

20 Retrosynthetic Analysis of (-)-Calyciphylline N (1) 20

21 Completion of the Synthesis of (-)-Calyciphylline N (1) 21

22 Completion of the Synthesis of (-)-Calyciphylline N (1) 22

23 Completion of the Synthesis of (-)-Calyciphylline N (1) 23

24 Completion of the Synthesis of (-)-Calyciphylline N (1) 24

25 Completion of the Synthesis of (-)-Calyciphylline N (1) 25

26 Completion of the Synthesis of (-)-Calyciphylline N (1) 26

27 Completion of the Synthesis of (-)-Calyciphylline N (1) 27

28 Completion of the Synthesis of (-)-Calyciphylline N (1) 28

29 Completion of the Synthesis of (-)-Calyciphylline N (1) 29

30 Summary The first total synthesis of Longeracinphyllin A 20 steps, 5.09 % overall yield Ang Li. et al. J. Am. Chem. Soc. 2017, 139, The first total synthesis of ( )-calyciphylline N (1) 37 steps, 0.39 % overall yield Amos B. Smith, III. et al. J. Am. Chem. Soc. 2014, 136,

31 The First Paragraph Daphniphyllum alkaloids are a large family of polycyclic natural products (>300 members) isolated from the evergreen plants of the genus Daphniphyllum. They exhibit a wide range of biological activities, including antitumor, antiviral, and nerve growth factor-regulating properties, and attract considerable attention from the synthesis community. The groups of Heathcock, Carreira, Smith, Fukuyama, and ours have accomplished the syntheses of nine Daphniphyllum alkaloids (1 9, Figure 1). The calyciphylline A subfamily comprises more than 50 members, most of which share a characteristic hexacyclic core. Despite the intense efforts toward the synthesis of this subclass, the only member that has been synthesized to date is daphenylline (8, Figure 1) possessing a nonrepresentative arene-containing skeleton. 31

32 The First Paragraph Longeracinphyllin A (10, Figure 1) is a structural representative of the subfamily, which was isolated by Hao and co-workers from the leaves of Daphniphyllum longeracemosum. Its six consecutive stereocenters including the vicinal quaternary centers pose a challenge for chemical synthesis. Herein, we report the first and asymmetric total synthesis of this alkaloid. 32

33 The Last Paragraph In summary, we have accomplished the first total synthesis of longeracinphyllin A (10). The decagram preparation of tetracycle 15, featuring silver-catalyzed alkyne cyclization and Luche radical cyclization, formed a basis of the synthesis. The sterically congested E ring containing vicinal tertiary and quaternary carbons was constructed through a Lu [3 + 2] cycloaddition reaction promoted by DPPF. The late intermediate 29 was prepared on a gram scale. These endeavors may facilitate the biological studies of this alkaloid and analogues thereof. 33

34 Acknowledgement 34