Nineteen-step total synthesis of (+)-phorbol

Nature

Volumn 532, Issue 7597, 2016, Pages 90-93

  Kawamura, Shuhei ^a   Chu, Hang ^a   Felding, Jakob ^b   Baran, Phil S ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b LEO PHARMA A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE DERIVATIVE; CYCLOPROPANE; KETONE DERIVATIVE; PHORBOL; 3-CARENE; BIOLOGICAL PRODUCT; DITERPENE; INGENANE; OXYGEN; PHORBOL DERIVATIVE; PHORBOL ESTER; TERPENE;

CHEMICAL PROPERTY; COMPLEXITY; ORGANIC COMPOUND; OXIDATION; OXYGEN; TERPENE;

ACUTE MYELOBLASTIC LEUKEMIA; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; COVALENT BOND; CYCLIZATION; DRUG SYNTHESIS; ENANTIOSELECTIVITY; MUKAIYAMA REACTION; OXIDATION; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; X RAY CRYSTALLOGRAPHY; CHEMICAL STRUCTURE; CHEMISTRY; ISOLATION AND PURIFICATION; METABOLISM; STEREOISOMERISM; SYNTHESIS;

BIOLOGICAL PRODUCTS; CHEMISTRY TECHNIQUES, SYNTHETIC; DITERPENES; MOLECULAR STRUCTURE; MONOTERPENES; OXYGEN; PHORBOL ESTERS; PHORBOLS; STEREOISOMERISM;

EID: 84963500354     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature17153     Document Type: Article

References (30)

1. Wang, H.-B., Wang, X.-Y., Liu, L.-P., Qin, G.-W. & Kang, T.-G. Tigliane diterpenoids from the euphorbiaceae and thymelaeaceae families. Chem. Rev. 115, 2975-3011 (2015).
2. Chen, K. & Baran, P. S. Total synthesis of eudesmane terpenes by site-selective C-H oxidations. Nature 459, 824-828 (2009).
3. Foo, K., et al. Scalable, enantioselective synthesis of germacrenes and related sesquiterpenes inspired by terpene cyclase phase logic. Angew. Chem. Int. Ed. 51, 11491-11495 (2012).
4. Mendoza, A., Ishihara, Y. & Baran, P. S. Scalable enantioselective total synthesis of taxanes. Nature Chem. 4, 21-25 (2012).
5. Wilde, N. C., Isomura, M., Mendoza, A. & Baran, P. S. Two-phase synthesis of (-)-taxuyunnanine D. J. Am. Chem. Soc. 136, 4909-4912 (2014).
6. Jrgensen, L., et al. 14-step synthesis of (-)-ingenol from (+)-3-carene. Science 341, 878-882 (2013).
7. McKerrall, S. J., Jrgensen, L., Kuttruff, C. A., Ungeheuer, F. & Baran, P. S. Development of a concise synthesis of (-)-ingenol. J. Am. Chem. Soc. 136, 5799-5810 (2014).
8. Jin, Y., et al. C-H oxidation of ingenanes enables potent and selective protein kinase C isoform activation. Angew. Chem. Int. Ed. 54, 14044-14048 (2015).
9. Isakov, N. & Altman, A. Regulation of immune system cell functions by protein kinase C. Front. Immunol. 4, 384 (2013).
10. McKernan, L. N., Momjian, D. & Kulkosky, J. Protein kinase C: one pathway towards the eradication of latent HIV-1 reservoirs. Adv. Virol. 2012, 805347 (2012).
11. Mackay, H. J. & Twelves, C. J. Targeting the protein kinase C family: are we there yet? Nature Rev. Cancer 7, 554-562 (2007); corrigendum 8, doi:10.1038/nrc2350 (2008).
12. Wender, P. A., et al. Studies on tumor promoters. 8. The synthesis of phorbol. J. Am. Chem. Soc. 111, 8957-8958 (1989).
13. Wender, P. A., Lee, H. Y., Wilhelm, R. S. & Williams, P. D. Studies on tumor promoters. 7. The synthesis of a potentially general precursor of the tiglianes, daphnanes, and ingenanes. J. Am. Chem. Soc. 111, 8954-8957 (1989).
14. Wender, P. A., Rice, K. D. & Schnute, M. E. The first formal asymmetric synthesis of phorbol. J. Am. Chem. Soc. 119, 7897-7898 (1997).
15. Wender, P. A. & McDonald, F. E. Studies on tumor promoters. 9. A secondgeneration synthesis of phorbol. J. Am. Chem. Soc. 112, 4956-4958 (1990).
16. Lee, K. & Cha, J. K. Formal synthesis of (+)-phorbol. J. Am. Chem. Soc. 123, 5590-5591 (2001).
17. Sugita, K., Shigeno, K., Neville, C. F., Sasai, H. & Shibasaki, M. Synthetic studies towards phorbols: synthesis of B or C ring substituted phorbol skeletons in the naturally occurring form. Synlett 1994, 325-329 (1994).
18. Sugita, K., Neville, C. F., Sodeoka, M., Sasai, H. & Shibasaki, M. Stereocontrolled syntheses of phorbol analogs and evaluation of their binding affinity to PKC. Tetrahedr. Lett. 36, 1067-1070 (1995).
19. Newhouse, T. & Baran, P. S. If C-H bonds could talk: selective C-H bond oxidation. Angew. Chem. Int. Ed. 50, 3362-3374 (2011).
20. Zou, L., et al. Enhanced reactivity in dioxirane C-H oxidations via strain release: a computational and experimental study. J. Org. Chem. 78, 4037-4048 (2013).
21. Michaudel, Q., et al. Improving physical properties via C-H oxidation: chemical and enzymatic approaches. Angew. Chem. Int. Ed. 53, 12091-12096 (2014).
22. McCormick, J. P. & Barton, D. L. Synthetic applications of metal halides. Conversion of cyclopropylmethanols into homoallylic halides. J. Org. Chem. 45, 2566-2570 (1980).
23. Miyoshi, N., Takeuchi, S. & Ohgo, Y. A facile synthesis of 2,3-dihydroxyketones from 1,2-diketones and aldehydes using samarium diiodide. Chem. Lett. 22, 959-962 (1993).
24. Krohn, K., Frese, P. & Florke, U. Biomimetic synthesis of the racemic angucyclinones of the aquayamycin and WP 3688-2 Types. Chemistry 6, 3887-3896 (2000).
25. Bartsch, H. & Hecker, E. Zur chemie des phorbols, XIII. Uber eine acyloinumlagerung des 12-desoxy-12-oxo-phorbol-13.20-diacetats. Liebigs Ann. Chem. 725, 142-153 (1969).
26. Salmond, W. G., Barta, M. A. & Havens, J. L. Allylic oxidation with 3,5-dimethylpyrazole. Chromium trioxide complex. Steroidal 5-7-ketones. J. Org. Chem. 43, 2057-2059 (1978).
27. Sha, C.-K. & Huang, S.-J. Synthesis of β-substituted a-iodocycloalkenones. Tetrahedr. Lett. 36, 6927-6928 (1995).
28. Stille, J. K. The palladium-catalyzed cross-coupling reactions of organotin reagents with organic electrophiles. Angew. Chem. Int. Ed. Engl. 25, 508-524 (1986).
29. Nicolaou, K. C. & Sorensen, E. J. Classics in Total Synthesis: Targets, Strategies, Methods 821 (Wiley, 1996).
30. Gutekunst, W. R. & Baran, P. S. C-H functionalization logic in total synthesis. Chem. Soc. Rev. 40, 1976-1991 (2011).