A Computational Investigation of the Uncatalysed and Water-Catalysed Acyl Rearrangements in Ingenol Esters*
Asja A. Kroeger A and Amir Karton A B
+ Author Affiliations
- Author Affiliations
A School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia.
B Corresponding author. Email: amir.karton@uwa.edu.au
Australian Journal of Chemistry 71(4) 212-221 https://doi.org/10.1071/CH17501
Submitted: 12 September 2017 Accepted: 18 October 2017 Published: 23 November 2017
Abstract
Ingenol esters have been identified as potent anticancer and HIV latency reversing agents. Ingenol-3-angelate was recently approved as a topical treatment for precancerous actinic keratosis skin lesions. It was found, however, that ingenol esters can undergo a series of acyl rearrangements, which may affect their biological potency and the shelf-life of drug formulations. We use double-hybrid density functional theory to explore the mechanisms for the uncatalysed and water-catalysed acyl migrations in a model ingenol ester. The uncatalysed reaction may proceed either via a concerted mechanism or via a stepwise mechanism that involves a chiral orthoester intermediate. We find that the stepwise pathway is kinetically preferred by a significant amount of ΔΔH‡298 = 44.5 kJ mol−1. The uncatalysed 3-O-acyl to 5-O-acyl and 5-O-acyl to 20-O-acyl stepwise rearrangements involve cyclisation and ring-opening steps, both concomitant with a proton transfer. We find that the ring-opening step is the rate-determining step for both rearrangements, with reaction barrier heights of ΔH‡298 = 251.6 and 177.1 kJ mol−1 respectively. The proton transfers in the cyclisation and ring-opening steps may be catalysed by a water molecule. The water catalyst reduces the reaction barrier heights of these steps by over 90 kJ mol−1.
References
[1] W. Adolf, H. Opferkuch, E. Hecker, Fette, Seifen, Anstrichm. 1968, 70, 825.| Crossref | GoogleScholarGoogle Scholar |
[2] G. Appendino, in Progress in the Chemistry of Organic Natural Products (Eds A. Kinghorn, H. Falk, S. Gibbons, J. Kobayashi) 2016, Vol. 102, pp. 1–90 (Springer International Publishing: Basel, Switzerland).
[3] D. Weedon, J. Chick, Med. J. Aust. 1976, 1, 928.
| 1:STN:280:DyaE2s%2FjsVSksA%3D%3D&md5=d405e02936e927ec30bb409eb753047fCAS |
[4] S. M. Ogbourne, P. G. Parsons, Fitoterapia 2014, 98, 36.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtlantLjO&md5=69e7c8b5eb28a89acf911b6cf35d4912CAS |
[5] A. Vasas, D. Rédei, D. Csupor, J. Molnár, J. Hohmann, Eur. J. Org. Chem. 2012, 5115.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1aktLfL&md5=b038fc04373cac33af8bf6eac752e1eeCAS |
[6] M. Fujiwara, K. Ijichi, K. Tokuhisa, K. Katsuura, G. Y. S. Wang, D. Uemura, S. Shigeta, K. Konno, T. Yokota, M. Baba, Antivir. Chem. Chemother. 1996, 7, 230.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XlvFCntrg%3D&md5=ef8df96ec4767ba918be5cd324cdb55cCAS |
[7] P. Hampson, H. Chahal, F. Khanim, R. Hayden, A. Mulder, L. K. Assi, C. M. Bunce, J. M. Lord, Blood 2005, 106, 1362.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXosVejt7s%3D&md5=8cc31c938c36c53a0ca5235d52ef1124CAS |
[8] G. Appendino, G. C. Tron, G. Cravotto, G. Palmisano, R. Annunziata, G. Baj, N. Surico, Eur. J. Org. Chem. 1999, 3413.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXnslSgtLs%3D&md5=bd42ddb6d3d5df7377c22327b03100d9CAS |
[9] G. Darcis, A. Kula, S. Bouchat, K. Fujinaga, F. Corazza, A. Ait-Ammar, N. Delacourt, A. Melard, K. Kabeya, C. Vanhulle, B. Van Driessche, J.-S. Gatot, T. Cherrier, L. F. Pianowski, L. Gama, C. Schwartz, J. Vila, A. Burny, N. Clumeck, M. Moutschen, S. De Wit, B. M. Peterlin, C. Rouzioux, O. Rohr, C. Van Lint, PLoS Pathog. 2015, 11, e1005063.
| Crossref | GoogleScholarGoogle Scholar |
[10] J. Brogdon, W. Ziani, X. Wang, R. S. Veazey, H. Xu, Sci. Rep. 2016, 6, 39032.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XitFGjsrfM&md5=b34c821377e19943645ab908dbeee359CAS |
[11] G. Jiang, E. A. Mendes, P. Kaiser, S. Sankaran-Walters, Y. Tang, M. G. Weber, G. P. Melcher, G. R. I. Thompson, A. Tanuri, L. F. Pianowski, J. K. Wong, S. Dandekar, AIDS 2014, 28, 1555.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhslWiur%2FN&md5=5e811d6a6ae56a4e18ce74f2c508d389CAS |
[12] S. V. Vemula, J. W. Maxwell, A. Nefedov, B.-L. Wan, J. Steve, W. Newhard, R. I. Sanchez, D. Tellers, R. J. Barnard, W. Blair, D. Hazuda, A. L. Webber, B. J. Howell, Antiviral Res. 2017, 139, 161.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXht1agurY%3D&md5=2f409db0486b7a5efaeef0808be626d1CAS |
[13] C. M. Abreu, S. L. Price, E. N. Shirk, R. D. Cunha, L. F. Pianowski, J. E. Clements, PLoS One 2014, 9, e97257.
| Crossref | GoogleScholarGoogle Scholar |
[14] X. Liang, G. Grue-Sørensen, K. Månsson, P. Vedsø, A. Soor, M. Stahlhut, M. Bertelsen, K. M. Engell, T. Högberg, Bioorg. Med. Chem. Lett. 2013, 23, 5624.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtlOru73J&md5=11680786d2dafaf485d44bce50d7f6bfCAS |
[15] M. B. Brown, M. E. D. Crothers, T. Nazir, WO Patent Appl. No. 2007068963 2007.
[16] P. O. Arvidsson, E. Farkas, K. Petersson, G. Hoy, US Patent Appl. No. US20140350120 A1 2014.
[17] M. Bertelsen, M. Stahlhut, G. Grue-Sørensen, X. Liang, G. B. Christensen, K. Skak, K. M. Engell, T. Högberg, Dermatol. Ther. 2016, 6, 599.
| Crossref | GoogleScholarGoogle Scholar |
[18] G. Grue-Sørensen, X. Liang, K. Månsson, P. Vedsø, M. Dahl Sørensen, A. Soor, M. Stahlhut, M. Bertelsen, K. M. Engell, T. Högberg, Bioorg. Med. Chem. Lett. 2014, 24, 54.
| Crossref | GoogleScholarGoogle Scholar |
[19] L. Brecker, M. Mahut, A. Schwarz, B. Nidetzky, Magn. Reson. Chem. 2009, 47, 328.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjvVOhtbw%3D&md5=cdd95a7d4b769d74c69fc8ca06089217CAS |
[20] S. J. Vanderhoeven, J. C. Lindon, J. Troke, G. E. Tranter, I. D. Wilson, J. K. Nicholson, Xenobiotica 2004, 34, 73.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtlGjurg%3D&md5=97722b99920c3e1a8f03dd0bb455035fCAS |
[21] N. G. Berry, L. Iddon, M. Iqbal, X. Meng, P. Jayapal, C. H. Johnson, J. K. Nicholson, J. C. Lindon, J. R. Harding, I. D. Wilson, A. V. Stachulski, Org. Biomol. Chem. 2009, 7, 2525.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXnvV2ns7k%3D&md5=a435d03175a3bcd134027f84bb1b83ecCAS |
[22] M. U. Roslund, O. Aitio, J. Wärnå, H. Maaheimo, D. Y. Murzin, R. Leino, J. Am. Chem. Soc. 2008, 130, 8769.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXntVygsbs%3D&md5=c50a2f2469a388399317b87e7ded2f8bCAS |
[23] H. Bundgaard, J. Hansen, Int. J. Pharm. 1981, 7, 197.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3MXhvVSmtbY%3D&md5=abdd4dc3c3f326d98b68857a15039a29CAS |
[24] A. M. Fureby, C. Virto, P. Adlercreutz, B. Mattiasson, Biocatal. Biotransform. 1996, 14, 89.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXpt1aqug%3D%3D&md5=d195ea1db0484359c9fb733eb18408ffCAS |
[25] T. Horrobin, C. H. Tran, D. Crout, J. Chem. Soc., Perkin Trans. 1 1998, 1069.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXhsVyku7o%3D&md5=33bab2472ca7dde6b241664f7562d2b9CAS |
[26] R. M. Rowell, Carbohydr. Res. 1972, 23, 417.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE38XltVaisLo%3D&md5=9a4c74f11abfd493c37c9fcb5eb0da2bCAS |
[27] G. J. F. Chittenden, J. G. Buchanan, Carbohydr. Res. 1969, 11, 379.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE3cXjs1Oi&md5=ec1782c3307e491a9f462bf58172a39bCAS |
[28] T. Lassila, J. Hokkanen, S.-M. Aatsinki, S. Mattila, M. Turpeinen, A. Tolonen, Chem. Res. Toxicol. 2015, 28, 2292.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXitVSgurfL&md5=545058040c43d54b8227ad1e412f2cafCAS |
[29] A. V. Stachulski, J. R. Harding, J. C. Lindon, J. L. Maggs, B. K. Park, I. D. Wilson, J. Med. Chem. 2006, 49, 6931.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1Gls7jP&md5=6b15d429aa139f1e7fe14f9b44ed6396CAS |
[30] A. Iwamura, M. Nakajima, S. Oda, T. Yokoi, Drug Metab. Pharmacokinet. 2017, 32, 2.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhvFKjs7zE&md5=6722c37006ffba9b28c0104462037e22CAS |
[31] D. L. Compton, J. A. Laszlo, M. Appell, K. E. Vermillion, K. O. Evans, J. Am. Oil Chem. Soc. 2012, 89, 2259.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhs12mu7vO&md5=c6ee0659ffdb56757af2031fe5aab146CAS |
[32] D. L. Compton, J. A. Laszlo, M. Appell, K. E. Vermillion, K. O. Evans, J. Am. Oil Chem. Soc. 2014, 91, 271.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsleksrrI&md5=afe4002bbcaf74785ad4ce0137607755CAS |
[33] M. A. Rangelov, G. N. Vayssilov, D. D. Petkov, Int. J. Quantum Chem. 2006, 106, 1346.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XislOku78%3D&md5=f1d1b347147644ff1c798daa5e8c58c9CAS |
[34] A. P. Doerschuk, J. Am. Chem. Soc. 1952, 74, 4202.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG2cXivVGjuw%3D%3D&md5=bd1c77c1d16448f2a5a3c13d40bb5365CAS |
[35] C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXktFWrtbw%3D&md5=a4fd99b0357ab941e5799cbcb338fdb2CAS |
[36] A. D. Becke, J. Chem. Phys. 1993, 98, 5648.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXisVWgtrw%3D&md5=cd069e9165ffddacc154f2d6ee26a63bCAS |
[37] P. J. Stephens, F. J. Devlin, C. F. Chabalowski, M. J. Frisch, J. Phys. Chem. 1994, 98, 11623.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXmvVSitbY%3D&md5=bbf11b61d118c610f2c097c0395e80d8CAS |
[38] S. Grimme, S. Ehrlich, L. Goerigk, J. Comput. Chem. 2011, 32, 1456.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjsF2isL0%3D&md5=c7e7bf511d3849933ce9ab19fcf3353aCAS |
[39] J. A. Pople, M. Head-Gordon, K. Raghavachari, J. Chem. Phys. 1987, 87, 5968.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXislSqsw%3D%3D&md5=ff938406e91c1e29a40406dbb528aab7CAS |
[40] R. Krishnan, J. S. Binkley, R. Seeger, J. A. Pople, J. Chem. Phys. 1980, 72, 650.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3cXpvFyitA%3D%3D&md5=caea7d3979dfad320c358509e9cbca51CAS |
[41] A. D. McLean, G. S. Chandler, J. Chem. Phys. 1980, 72, 5639.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3cXksFCnu7c%3D&md5=cfa4faa9ecbf204e77864e04796fdd5dCAS |
[42] S. Grimme, J. Antony, S. Ehrlich, H. Krieg, J. Chem. Phys. 2010, 132, 154104.
| Crossref | GoogleScholarGoogle Scholar |
[43] S. Grimme, WIREs Comput. Mol. Sci. 2011, 1, 211.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXksVGlu70%3D&md5=50eca88efffd9f2b2a20bf3e6af30a40CAS |
[44] A. D. Becke, E. R. Johnson, J. Chem. Phys. 2005, 123, 154101.
| Crossref | GoogleScholarGoogle Scholar |
[45] A. V. Marenich, C. J. Cramer, D. G. Truhlar, J. Phys. Chem. B 2009, 113, 6378.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXksV2is74%3D&md5=13d1f1c69d0057e107d895f3c22210a2CAS |
[46] C. Gonzalez, H. B. Schlegel, J. Chem. Phys. 1989, 90, 2154.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXhsVahtbk%3D&md5=75414cbbb9efa65d0bc8c177e808fb17CAS |
[47] C. Gonzalez, H. B. Schlegel, J. Chem. Phys. 1990, 94, 5523.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXktl2rt78%3D&md5=66d8150cbec8983122fb3bca1de1305fCAS |
[48] M. D. Hanwell, D. E. Curtis, D. C. Lonie, T. Vandermeersch, E. Zurek, G. R. Hutchison, J. Cheminform. 2012, 4, 17.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVGksLg%3D&md5=19e7f2e8202d54c83b1b34bb95e0152fCAS |
[49] L. Goerigk, S. Grimme, WIREs Comput. Mol. Sci. 2014, 4, 576.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhvVelu7jI&md5=142d2883f3d7e118d6736c10591819fbCAS |
[50] S. Kozuch, J. M. L. Martin, J. Comput. Chem. 2013, 34, 2327.
| 1:CAS:528:DC%2BC3sXhtlans7fN&md5=51f852b59074cbc11a27eabda3fdd19fCAS |
[51] S. Kozuch, J. M. L. Martin, Phys. Chem. Chem. Phys. 2011, 13, 20104.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsVCgurbF&md5=a7cde66784de498febfaa80245d1cf92CAS |
[52] A. Karton, A. Tarnopolsky, J.-F. Lamere, G. C. Schatz, J. M. L. Martin, J. Phys. Chem. A 2008, 112, 12868.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVSnt7vI&md5=c6fa3c38ad72bac11d7cf200cfc69fb1CAS |
[53] A. Tarnopolsky, A. Karton, R. Sertchook, D. Vuzman, J. M. L. Martin, J. Phys. Chem. A 2008, 112, 3.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVegu7vO&md5=168e289196df53b3472c7e92af4127e7CAS |
[54] A. Karton, R. J. O’Reilly, L. Radom, J. Phys. Chem. A 2012, 116, 4211.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XlsVaktrk%3D&md5=83c2781c48e01bf8c2fc2c400e3c87e9CAS |
[55] L. Goerigk, A. Karton, J. M. L. Martin, L. Radom, Phys. Chem. Chem. Phys. 2013, 15, 7028.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXmsVaqsL8%3D&md5=5cb49345bed3fa8b34efccc9e9176a23CAS |
[56] A. Karton, L. Goerigk, J. Comput. Chem. 2015, 36, 622.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXjt1Sgurc%3D&md5=97f7e010580e2505b9fa14e98721d8d6CAS |
[57] L.-J. Yu, F. Sarrami, R. J. O’Reilly, A. Karton, Chem. Phys. 2015, 458, 1.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhtFOju7vN&md5=a1bf4f1165ffc25595f3a39b31b1eb4cCAS |
[58] F. Weigend, R. Ahlrichs, Phys. Chem. Chem. Phys. 2005, 7, 3297.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXpsFWgu7o%3D&md5=7e176a704125fa22ee6e2e2a691ef7fdCAS |
[59] Y. Zhao, N. E. Schultz, D. G. Truhlar, J. Chem. Theory Comput. 2006, 2, 364.
| Crossref | GoogleScholarGoogle Scholar |
[60] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, et al., Gaussian 09, Revision E.01 2009 (Gaussian Inc.: Wallingford, CT).
[61] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, G. A. Petersson, H. Nakatsuji, et al., Gaussian 16, Revision A.03 2016 (Gaussian Inc.: Wallingford, CT).
[62] J. P. Foster, F. Weinhold, J. Am. Chem. Soc. 1980, 102, 7211.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3cXmtFSmsbw%3D&md5=b652456b76f5c68208e330dda4bdde5fCAS |
[63] F. Weinhold, in Encyclopedia of Computational Chemistry (Eds P. v. R. Schleyer, N. L. Allinger, T. Clark, J. Gasteiger, P. A. Kollman, H. F. Schaefer III, P. R. Schreiner) 1998, Vol. 3, pp. 1792–1811 (John Wiley & Sons: Chichester).
[64] E. D. Glendening, C. R. Landis, F. Weinhold, WIREs Comput. Mol. Sci. 2012, 2, 1.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvFGls7w%3D&md5=9903f478ebde5e3f2733a7f410eb66e9CAS |
[65] J. E. D. Glendening, K. Badenhoop, A. E. Reed, J. E. Carpenter, J. A. Bohmann, C. M. Morales, C. R. Landis, F. Weinhold, NBO6 2013 (Theoretical Chemistry Institute, University of Wisconsin: Madison, WI).
[66] B. Gold, N. E. Shevchenko, N. Bonus, G. B. Dudley, I. V. Alabugin, J. Org. Chem. 2012, 77, 75.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsVGkt7jE&md5=3beee6d8163cda696259117fd7ab795dCAS |
[67] I. V. Alabugin, K. M. Gilmore, P. W. Peterson, WIREs Comput. Mol. Sci. 2011, 1, 109.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXksVKjsb8%3D&md5=5e659ff055370ce7ee1c3539caa7786bCAS |
[68] M. P. Freitas, Org. Biomol. Chem. 2013, 11, 2885.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXltl2is7o%3D&md5=a09d3bc94bb358b63a51ed50cf95cf6cCAS |
[69] I. V. Alabugin, T. A. Zeidan, J. Am. Chem. Soc. 2002, 124, 3175.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhsF2isrw%3D&md5=6df50aa1ba05a729ade7ce16ba6b8667CAS |
[70] B. Gold, G. B. Dudley, I. V. Alabugin, J. Am. Chem. Soc. 2013, 135, 1558.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXitFan&md5=a85a39610815b511b7c8367517c4468aCAS |
[71] H. B. Bürgi, J. D. Dunitz, E. Shefter, J. Am. Chem. Soc. 1973, 95, 5065.
| Crossref | GoogleScholarGoogle Scholar |
[72] H. B. Bürgi, E. Shefter, J. D. Dunitz, Tetrahedron 1975, 31, 3089.
| Crossref | GoogleScholarGoogle Scholar |
[73] A. Karton, Chem. Phys. Lett. 2014, 592, 330.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtlems70%3D&md5=60f01dcd3502f1e14757430a438d935fCAS |
[74] A. Karton, R. J. O’Reilly, B. Chan, L. Radom, J. Chem. Theory Comput. 2012, 8, 3128.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtFGhsrvE&md5=7c39e6eea31dae029fc3687286b8166bCAS |
[75] L. Vereecken, J. S. Francisco, Chem. Soc. Rev. 2012, 41, 6259.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhtlaktr%2FK&md5=38599e0c443f090148be9a3643301c39CAS |
[76] E. Vöhringer-Martinez, B. Hansmann, H. Hernandez, J. S. Francisco, J. Troe, B. Abel, Science 2007, 315, 497.
| Crossref | GoogleScholarGoogle Scholar |
[77] G. da Silva, Angew. Chem. Int. Ed. 2010, 49, 7523.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlGit7nM&md5=628272e87c103391733f481d46ce34c8CAS |
[78] R. S. Assary, P. C. Redfern, J. Greeley, L. A. Curtiss, J. Phys. Chem. B 2011, 115, 4341.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjvFaktr8%3D&md5=83df3bc67cbb1fbd5bbdbd8cc97cbef6CAS |
[79] M. Miljkovic, Carbohydrates: Synthesis, Mechanisms, and Stereoelectronic Effects 2010 (Springer: New York, NY).
[80] The boat conformation in this transition structure is accessible owing to the rotational freedom of the 1° 20-hydroxyl group participating in the rearrangement as well as the comparably lower steric hindrance from the ingenol backbone and minimises steric repulsion experienced by the 20-CH2 group. As in the remaining transition structures of pathways a and c, in chair conformations, the breaking C=O substituent is in pseudo-axial position while the hydrogen atom has a pseudo-equatorial orientation, allowing the same stereoelectronic interactions elaborated below.
[81] J. Edward, Chem. Ind. 1955, 1102.
| 1:CAS:528:DyaG28XntFKq&md5=8a36efde722da2964f6d60608f8fdd4aCAS |
[82] R. U. Lemieux, P. Chu, 133rd National Meeting of the American Chemical Society 31N 1958 (American Chemical Society: Washington, DC).
[83] G. R. J. Thatcher, The Anomeric Effect and Associated Stereoelectronic Effects 1993 (American Chemical Society: Washington, DC).
[84] K. Omoto, K. Marusaki, H. Hirao, M. Imade, H. Fujimoto, J. Phys. Chem. A 2000, 104, 6499.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjvFKqtb8%3D&md5=84a338dafc6a72b4510aba0e392129d4CAS |
[85] L. Carballeira, I. Pérez-Juste, J. Org. Chem. 1997, 62, 6144.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXlvFSrtbg%3D&md5=9f1767bb0fcebc03e54955ffbc38c481CAS |
[86] N. Hasanzadeh, D. Nori-Shargh, H. Yahyaei, S. N. Mousavi, S. Kamrava, J. Phys. Chem. A 2017, 121, 5548.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXhtVygtbrM&md5=3da056abe2b175c3e26a0fe0cbc3cbf5CAS |
[87] L. Radom, W. J. Hehre, J. A. Pople, J. Am. Chem. Soc. 1972, 94, 2371.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE38XhsFeju7w%3D&md5=2475c3ee5a37e460cb428fe2020ec3dcCAS |
[88] Y. Mo, Nat. Chem. 2010, 2, 666.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXpt1aksb8%3D&md5=45b6d4d7f5799f59ad59433f591a2a87CAS |
[89] E. J. Cocinero, P. Çarçabal, T. D. Vaden, J. P. Simons, B. G. Davis, Nature 2011, 469, 76.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXisVSnsw%3D%3D&md5=a4b55646c364073f328d61df9937a907CAS |
[90] C. M. Filloux, Angew. Chem. Int. Ed. 2015, 54, 8880.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhtVOmu73F&md5=da0bc556f9a5df9cb3a0ab1038f44430CAS |
[91] E. Juaristi, R. Notario, J. Org. Chem. 2016, 81, 1192.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XptlGgsQ%3D%3D&md5=3fd9e955326a9d312e8c22472d3016beCAS |
[92] D. Nori-Shargh, S. N. Mousavi, R. Tale, H. Yahyaei, Struct. Chem. 2016, 27, 1753.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhtFamtL3I&md5=e70aa92d061ce5056291840414f4c1d3CAS |
[93] G. A. Jeffrey, J. A. Pople, J. S. Binkley, S. Vishveshwara, J. Am. Chem. Soc. 1978, 100, 373.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1cXkt1Cksr0%3D&md5=ee0f1f9959fc69e7b60a7d31fcf4d282CAS |
[94] E. Juaristi, R. Notario, J. Org. Chem. 2015, 80, 2879.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXivFWjsrg%3D&md5=8792c27013f4bdbc820db4da5ba1a928CAS |
[95] See pp. 236–256 in: I. V. Alabugin, Stereoelectronic Effects: A Bridge Between Structure and Reactivity 2016 (John Wiley & Sons, Ltd: Chichester, UK).
[96] W. Yang, D. G. Drueckhammer, J. Am. Chem. Soc. 2001, 123, 11004.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXntlGru70%3D&md5=2634b4ac3852cac527e83cebc0f4399aCAS |
