TY - JOUR A1 - Pagani, Alberto A1 - Gaeta, Simone A1 - Savchenko, Andrei I. A1 - Williams, Craig M. A1 - Appendino, Giovanni T1 - An improved preparation of phorbol from croton oil JF - Beilstein Journal of Organic Chemistry PY - 2017/// VL - 13 SP - 1361 EP - 1367 SN - 1860-5397 DO - 10.3762/bjoc.13.133 PB - Beilstein-Institut JA - Beilstein J. Org. Chem. UR - https://doi.org/10.3762/bjoc.13.133 KW - croton oil KW - diterpenoids KW - natural products KW - phorbol KW - transesterification N2 - Background: Croton oil is the only commercial source of the diterpenoid phorbol (1a), the starting material for the semi-synthesis of various diesters extensively used in biomedical research to investigate cell function and to evaluate in vivo anti-inflammatory activity. While efficient chemoselective esterification protocols have been developed for phorbol, its isolation from croton oil is technically complicated, and involves extensive manipulation of very toxic materials like the oil or its native diterpenoid fraction.Results: The preparation of a crude non-irritant phorboid mixture from croton oil was telescoped to only five operational steps, and phorbol could then be purified by gravity column chromatography and crystallization. Evidence is provided that two distinct phorboid chemotypes of croton oil exist, differing in the relative proportion of type-A and type-B esters and showing different stability to deacylation.Conclusion: The isolation of phorbol from croton oil is dangerous because of the toxic properties of the oil, poorly reproducible because of differences in its phorboid profile, and time-consuming because of the capricious final crystallization step. A solution for these issues is provided, suggesting that the poor-reproducibility of croton oil-based anti-inflammatory assays are the result of poor quality and/or inconsistent composition of croton oil. ER - TY - CHAP AU - Gläser, S. AU - Winter, A. AU - Hecker, E. T2 - Crotonis oleum (Crotonöl) T1 - Hagers Handbuch der Pharmazeutischen Praxis PY - 1998/// SP - 471 EP - 476 PB - Springer CY - Berlin A2 - Blaschek, W. A2 - Hänsel, R. A2 - Keller, K. A2 - Reichling, J. A2 - Rimpler, H. A2 - Schneider, G. ER - TY - JOUR AU - Meyer-Bertenrath, J. G. JF - Experientia PY - 1969/// VL - 25 SP - 1 EP - 5 DO - 10.1007/BF01903855 ER - TY - JOUR AU - Orra, S. AU - Waltzman, J. T. AU - Mlynek, K. AU - Duraes, E. F. R. AU - Kundu, N. AU - Zins, J. E. JF - Plast. Reconstr. Surg. PY - 2015/// VL - 136 SP - 99 EP - 100 DO - 10.1097/01.prs.0000472401.26529.67 ER - TY - JOUR AU - Pelletier, J. AU - Caventou, J. B. JF - J. Pharm. PY - 1818/// VL - 4 SP - 289 EP - 314 ER - TY - JOUR AU - Böhm, R. AU - Flaschenträger, B. JF - Naunyn-Schmiedeberg's Arch. Pharmacol. PY - 1930/// VL - 157 SP - 115 EP - 123 DO - 10.1007/BF01972119 ER - TY - JOUR AU - Hecker, E. AU - Schmidt, R. JF - Prog. Chem. Org. Nat. Prod. PY - 1974/// VL - 31 SP - 378 EP - 467 ER - TY - JOUR AU - Pettersen, R. C. AU - Ferguson, G. AU - Crombie, L. AU - Games, M. L. AU - Pointer, D. J. JF - Chem. Commun. PY - 1967/// SP - 716 EP - 717 DO - 10.1039/c19670000716 ER - TY - JOUR AU - Berenblum, I. JF - Cancer Res. PY - 1941/// VL - 1 SP - 44 EP - 48 ER - TY - JOUR AU - Newton, A. C. JF - Chem. Rev. PY - 2001/// VL - 101 SP - 2353 EP - 2364 DO - 10.1021/cr0002801 ER - TY - ELEC UR - http://www.lclabs.com/products/P-1680?gclid=CNeX-ZP4ocwCFaoy0wodPhsAOg ER - TY - JOUR AU - Han, Z. T. AU - Zhu, X. X. AU - Yang, R. Y. AU - Sun, J. Z. AU - Tian, G. F. AU - Liu, X. J. AU - Cao, G. S. AU - Newmark, H. L. AU - Conney, A. H. AU - Chang, R. L. JF - Proc. Natl. Acad. Sci. U. S. A. PY - 1998/// VL - 95 SP - 5357 EP - 5361 DO - 10.1073/pnas.95.9.5357 ER - TY - JOUR AU - Appendino, G. JF - Prog. Chem. Org. Nat. Prod. PY - 2016/// VL - 102 SP - 1 EP - 90 DO - 10.1007/978-3-319-33172-0_1 ER - TY - JOUR AU - Boyle, G. M. AU - d'Souza, M. M. A. AU - Pierce, C. J. AU - Adams, R. A. AU - Cantor, A. S. AU - Johns, J. P. AU - Maslovskaya, L. AU - Gordon, V. A. AU - Reddell, P. W. AU - Parsons, P. G. JF - PLoS One PY - 2014/// VL - 9 SP - e108887 DO - 10.1371/journal.pone.0108887 ER - TY - JOUR AU - Crombie, L. AU - Games, M. L. AU - Pointer, D. J. JF - J. Chem. Soc. C PY - 1968/// SP - 1347 EP - 1362 DO - 10.1039/j39680001347 ER - TY - JOUR AU - Pieters, L. A. AU - Vlietnick, A. J. JF - Planta Med. PY - 1986/// VL - 52 SP - 465 EP - 468 DO - 10.1055/s-2007-969255 ER - TY - JOUR AU - Marshall, G. T. AU - Douglas Kinghorn, A. JF - J. Chromatogr. PY - 1981/// VL - 206 SP - 421 EP - 424 DO - 10.1016/S0021-9673(00)82560-1 ER - TY - JOUR AU - Mishra, N. C. AU - Estensen, R. D. AU - Abdel-Monem, M. M. JF - J. Chromatogr. PY - 1986/// VL - 369 SP - 435 EP - 439 DO - 10.1016/S0021-9673(00)90154-7 ER - TY - JOUR AU - Bertolini, T. M. AU - Giorgione, J. AU - Harvey, D. F. AU - Newton, A. C. JF - J. Org. Chem. PY - 2003/// VL - 68 SP - 5028 EP - 5036 DO - 10.1021/jo030029w ER - TY - JOUR AU - Cairnes, D. A. AU - Mirvish, S. S. AU - Wallcave, L. JF - Cancer Lett. PY - 1981/// VL - 14 SP - 85 EP - 91 DO - 10.1016/0304-3835(81)90013-6 ER - TY - JOUR AU - Seebach, D. AU - Thaler, A. AU - Beck, A. K. JF - Helv. Chim. Acta PY - 1989/// VL - 72 SP - 857 EP - 867 DO - 10.1002/hlca.19890720502 ER - TY - JOUR AU - Tseng, S.-S. AU - Van Duuren, B. L. AU - Solomon, J. J. JF - J. Org. Chem. PY - 1977/// VL - 42 SP - 3645 EP - 3649 DO - 10.1021/jo00443a002 ER - TY - JOUR AU - Schmidt, R. AU - Hecker, R. JF - Cancer Res. PY - 1975/// VL - 35 SP - 1375 EP - 1377 ER - TY - JOUR AU - Tubaro, A. AU - Dri, P. AU - Delbello, G. AU - Zilli, C. AU - Della Loggia, R. JF - Agents Actions PY - 1986/// VL - 17 SP - 347 EP - 349 DO - 10.1007/BF01982641 ER - TY - JOUR AU - Bauer, R. AU - Tittel, G. AU - Wagner, H. JF - Planta Med. PY - 1983/// VL - 48 SP - 10 EP - 16 DO - 10.1055/s-2007-969869 ER - TY - CHAP AU - Breuer, W. B. T1 - Deceptions of World War II PY - 2002/// SP - 189 EP - 190 PB - Wiley & Sons ER - TY - CHAP AU - Steinbeck, J. T1 - Dubious Battle PY - 2006/// SP - 99 PB - Penguin Books ER - TY - CHAP AU - Evans, F. I. T2 - Phorbol: Its Esters and Derivatives T1 - Naturally Occurring Phorbol Esters PY - 1986/// SP - 171 EP - 215 PB - CRC Press CY - Boca Raton, Florida A2 - Evans, F. J. ER -