Lessons and revelations from biomimetic syntheses


Lessons and revelations from biomimetic syntheses

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ABSTRACT Biomimetic synthesis describes the field of organic chemistry that aims to emulate the natural, biosynthetic processes toward natural products. As well as providing insight into how


molecules are formed in nature, the benefits of this approach to total synthesis are numerous and extend beyond the gains typical of traditional synthesis. For example, using biosynthetic


proposals to design a synthetic route can highlight alternative methods to the desired target. The pursuit of biomimetic syntheses also promotes the development of new reactions to prove or


disprove a biosynthetic proposal or to unravel mechanistic implications of a proposed biosynthesis and can lead to the identification of new natural products. Here we look at some recent


compelling examples and examine how biomimetic synthesis has led to the discovery of new procedures and principles that would not have been found by other approaches. Access through your


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REFERENCES * Bentley, R. & Bennett, J.W. Constructing polyketides: from Collie to combinatorial biosynthesis. _Annu. Rev. Microbiol._ 53, 411–446 (1999). CAS  PubMed  Google Scholar  *


Robinson, R. LXIII.–A synthesis of tropinone. _J. Chem. Soc. Trans._ 111, 762–768 (1917). CAS  Google Scholar  * Breslow, R. Biomimetic chemistry. _Chem. Soc. Rev._ 1, 553–580 (1972). CAS 


Google Scholar  * Barton, D.H.R. _Reason and Imagination: Reflections on Research in Organic Chemistry: Selected Papers of Derek H.R. Barton_. (World Scientific, 1996). Google Scholar  *


Taylor, S.K. Biosynthetic, biomimetic and related epoxide cyclizations. A review. _Org. Prep. Proced. Int._ 24, 245–284 (1992). CAS  Google Scholar  * Yoder, R.A. & Johnston, J.N. A case


study in biomimetic total synthesis: polyolefin carbocyclizations to terpenes and steroids. _Chem. Rev._ 105, 4730–4756 (2005). AN ELEGANT REVIEW THAT PUTS TERPENE AND STEROID BIOSYNTHETIC


RESEARCH, SPANNING MORE THAN 70 YEARS, INTO CONTEXT. CAS  PubMed  PubMed Central  Google Scholar  * Scholz, U. & Winterfeldt, E. Biomimetic synthesis of alkaloids. _Nat. Prod. Rep._ 17,


349–366 (2000). CAS  PubMed  Google Scholar  * Bulger, P.G., Bagal, S.K. & Marquez, R. Recent advances in biomimetic natural product synthesis. _Nat. Prod. Rep._ 25, 254–297 (2008). CAS


  PubMed  Google Scholar  * Brunoldi, E., Luparia, M., Porta, A., Zanoni, G. & Vidari, G. Biomimetic cyclizations of functionalized isoprenoid polyenes: a cornucopia of synthetic


opportunities. _Curr. Org. Chem._ 10, 2259–2282 (2006). CAS  Google Scholar  * Beaudry, C.M., Malerich, J.P. & Trauner, D. Biosynthetic and biomimetic electrocyclizations. _Chem. Rev._


105, 4757–4778 (2005). CAS  PubMed  Google Scholar  * de la Torre, M.C. & Sierra, M.A. Comments on recent achievements in biomimetic organic synthesis. _Angew. Chem. Int. Ed. Engl._ 43,


160–181 (2004). CAS  PubMed  Google Scholar  * Nicolaou, K.C., Zipkin, R.E. & Petasis, N.A. The endiandric acid cascade. Electrocyclizations in organic synthesis. 3. “Biomimetic”


approach to endiandric acids A-G. Synthesis of precursors. _J. Am. Chem. Soc._ 104, 5558–5560 (1982). CAS  Google Scholar  * Nicolaou, K.C., Petasis, N.A. & Zipkin, R.E. The endiandric


acid cascade. Electrocyclizations in organic synthesis. 4. “Biomimetic” approach to endiandric acids A-G. Total synthesis and thermal studies. _J. Am. Chem. Soc._ 104, 5560–5562 (1982). CAS


  Google Scholar  * Heathcock, C.H. The enchanting alkaloids of Yuzuriha. _Angew. Chem. Int. Ed. Engl._ 31, 665–681 (1992). Google Scholar  * Cherney, E.C. & Baran, P.S.


Terpenoid-alkaloids: their biosynthetic twist of fate and total synthesis. _Isr. J. Chem._ 51, 391–405 (2011). CAS  PubMed  PubMed Central  Google Scholar  * Baldwin, J.E. & Abraham, E.


The biosynthesis of penicillins and cephalosporins. _Nat. Prod. Rep._ 5, 129–145 (1988). CAS  PubMed  Google Scholar  * Lane, A.L. & Moore, B.S. A sea of biosynthesis: marine natural


products meet the molecular age. _Nat. Prod. Rep._ 28, 411–428 (2011). CAS  PubMed  Google Scholar  * Stork, G. William Summer Johnson, 1913–1995. in _Biographical Memoirs_ VOLS. 23–24,


182–197 (National Academy Press, 2001). Google Scholar  * Davis, E.M. & Croteau, R. Cyclization enzymes in the biosynthesis of monoterpenes, sesterpenes and diterpenes. _Top. Curr.


Chem._ 209, 53–95 (2000). CAS  Google Scholar  * Maimone, T.J. & Baran, P.S. Modern synthetic efforts toward biologically active terpenes. _Nat. Chem. Biol._ 3, 396–407 (2007). CAS 


PubMed  Google Scholar  * Chen, K. & Baran, P.S. Total synthesis of eudesmane terpenes by site-selective C-H oxidations. _Nature_ 459, 824–828 (2009). A REPORT DEMONSTRATING A TWO-PHASE


APPROACH TO TERPENOID SYNTHESIS, MODELED ON THEIR NATURAL BIOSYNTHESIS. CAS  PubMed  Google Scholar  * Chen, K., Isihara, Y., Galán, M.M. & Baran, P.S. Total synthesis of eudesmane


terpenes: cyclase phase. _Tetrahedron_ 66, 4738–4744 (2010). CAS  Google Scholar  * Ortiz de Montellano, P.R. Hydrocarbon hydroxylation by cytochrome P450 enzymes. _Chem. Rev._ 110, 932–948


(2010). CAS  PubMed  PubMed Central  Google Scholar  * Engelin, C.J. & Fristrup, P. Palladium catalyzed allylic C-H alkylation: a mechanistic perspective. _Molecules_ 16, 951–969 (2011).


CAS  PubMed  PubMed Central  Google Scholar  * Giri, R., Shi, B.-F., Engle, K.M., Maugel, N. & Yu, J.-Q. Transition metal-catalyzed C-H activation reactions: diastereoselectivity and


enantioselectivity. _Chem. Soc. Rev._ 38, 3242–3272 (2009). CAS  PubMed  Google Scholar  * Davies, H.M.L. & Manning, J.R. Catalytic C-H functionalization by metal carbenoid and nitrenoid


insertion. _Nature_ 451, 417–424 (2008). CAS  PubMed  PubMed Central  Google Scholar  * Newhouse, T. & Baran, P.S. If C-H bonds could talk: selective C-H bond oxidation. _Angew. Chem.


Int. Ed. Engl._ 50, 3362–3374 (2011). CAS  PubMed  PubMed Central  Google Scholar  * Chen, M.S. & White, M.C. A predictably selective aliphatic C-H oxidation reaction for complex


molecule synthesis. _Science_ 318, 783–787 (2007). CAS  PubMed  Google Scholar  * Isihara, Y. & Baran, P.S. Two-phase terpene total synthesis: historical perspective and application to


the Taxol® problem. _Synlett_ 1733–1745 (2010). * Lin, Y.-Y. et al. Isolation and structure of brevetoxin B from the “red tide” dinoflagellate _Ptychodiscus brevis_ (_Gymnodinium breve_).


_J. Am. Chem. Soc._ 103, 6773–6775 (1981). CAS  Google Scholar  * Paz, B. et al. Yessotoxins, a group of marine polyether toxins: an overview. _Mar. Drugs_ 6, 73–102 (2008). CAS  PubMed 


PubMed Central  Google Scholar  * Yasumoto, T., Bagnis, R. & Vernoux, J.P. Toxicity study on surgeonfishes-II. Properties of the principal water-soluble toxin. _Nippon Suisan Gakkaishi_


42, 359–365 (1976). CAS  Google Scholar  * Lewis, R.J. The changing face of ciguatera. _Toxicon_ 39, 97–106 (2001). CAS  PubMed  Google Scholar  * Nakanishi, K. The chemistry of brevetoxins:


a review. _Toxicon_ 23, 473–479 (1985). CAS  PubMed  Google Scholar  * Lee, M.S., Qin, G., Nakanishi, K. & Zagorski, M.G. Biosynthetic studies of brevetoxins, potent neurotoxins


produced by the dinoflagellate _Gymnodinium breve_. _J. Am. Chem. Soc._ 111, 6234–6241 (1989). CAS  Google Scholar  * Shimizu, Y. Biosynthesis and biotransformation of marine invertebrate


toxins. in _Natural Toxins: Animal, Plant, and Microbial_ (ed. J.B. Harris) 123 (Clarendon Press, 1986). Google Scholar  * Nicolaou, K.C. The total synthesis of brevetoxin B: A twelve-year


odyssey in organic synthesis. _Angew. Chem. Int. Ed. Engl._ 35, 588–607 (1996). IN THIS REVIEW, NICOLAOU RECALLS HIS PROPOSAL FOR THE BIOSYNTHESIS OF LADDER POLYETHERS, WHICH HE INCLUDED IN


A PROPOSAL TO THE NATIONAL INSTITUTES OF HEALTH IN 1982. Google Scholar  * Baldwin, J.E. Rules for ring closure. _J. Chem. Soc. Chem. Commun._ 734–736 (1976). * Vilotijevic, I. &


Jamison, T.F. Epoxide-opening cascades in the synthesis of polycyclic polyether natural products. _Angew. Chem. Int. Ed. Engl._ 48, 5250–5281 (2009). CAS  PubMed  PubMed Central  Google


Scholar  * Morten, C.J. & Jamison, T.F. Water overcomes methyl group directing effects in epoxide-opening cascades. _J. Am. Chem. Soc._ 131, 6678–6679 (2009). CAS  PubMed  PubMed Central


  Google Scholar  * Vilotijevic, I. & Jamison, T.F. Synthesis of marine polycyclic polyethers _via endo_-selective epoxide-opening cascades. _Mar. Drugs_ 8, 763–809 (2010). CAS  PubMed 


PubMed Central  Google Scholar  * Nakata, T. Total synthesis of marine polycyclic ethers. _Chem. Rev._ 105, 4314–4347 (2005). CAS  PubMed  Google Scholar  * Alvarez, E., Candenas, M.-L.,


Pérez, R., Ravelo, J.L. & Martín, J.D. Useful designs in the synthesis of _trans_-fused polyether toxins. _Chem. Rev._ 95, 1953–1980 (1995). CAS  Google Scholar  * Hoberg, J.O. Synthesis


of seven-membered oxacycles. _Tetrahedron_ 54, 12631–12670 (1998). CAS  Google Scholar  * Marmsäter, F.P. & West, F.G. New efficient iterative approaches to polycyclic ethers.


_Chemistry_ 8, 4346–4353 (2002). PubMed  Google Scholar  * Sasaki, M. & Fuwa, H. Convergent strategies for the total synthesis of polycyclic ether marine metabolites. _Nat. Prod. Rep._


25, 401–426 (2008). CAS  PubMed  Google Scholar  * Vilotijevic, I. & Jamison, T.F. Epoxide-opening cascades promoted by water. _Science_ 317, 1189–1192 (2007). THE FIRST _ENDO_


-SELECTIVE CASCADE OF POLYEPOXIDE OPENINGS THAT DID NOT USE DIRECTING GROUPS TO GUIDE THE REACTION PROCESS. CAS  PubMed  PubMed Central  Google Scholar  * Morten, C.J., Byers, J.A., Van


Dyke, A.R., Vilotijevic, I. & Jamison, T.F. The development of _endo_-selective epoxide-opening cascades in water. _Chem. Soc. Rev._ 38, 3175–3192 (2009). CAS  PubMed  PubMed Central 


Google Scholar  * Morten, C.J., Byers, J.A. & Jamison, T.F. Evidence that epoxide-opening cascades promoted by water are stepwise and become faster and more selective after the first


cyclization. _J. Am. Chem. Soc._ 133, 1902–1908 (2011). CAS  PubMed  PubMed Central  Google Scholar  * Byers, J.A. & Jamison, T.F. On the synergism between H2O and a tetrahydropyran


template in the regioselective cyclization of an epoxy alcohol. _J. Am. Chem. Soc._ 131, 6383–6385 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Heathcock, C.H. Nature knows best:


An amazing reaction cascade is uncovered by design and discovery. _Proc. Natl. Acad. Sci. USA_ 93, 14323–14327 (1996). CAS  PubMed  PubMed Central  Google Scholar  * Grube, A., Immel, S.,


Baran, P.S. & Köck, M. Massadine chloride: a biosynthetic precursor of massadine and stylissadine. _Angew. Chem. Int. Ed. Engl._ 46, 6721–6724 (2007). CAS  PubMed  Google Scholar  *


Köck, M., Grube, A., Seiple, I.B. & Baran, P.S. The pursuit of palau'amine. _Angew. Chem. Int. Ed. Engl._ 46, 6586–6594 (2007). PubMed  Google Scholar  * Kato, H. et al. Notoamides


A-D: prenylated indole alkaloids isolated from a marine-derived fungus, _Aspergillus_ sp. _Angew. Chem. Int. Ed. Engl._ 46, 2254–2256 (2007). CAS  PubMed  Google Scholar  * Grubbs, A.W.,


Artman, I.G.D., Tsukamoto, S. & Williams, R.M. A concise total synthesis of the notoamides C and D. _Angew. Chem. Int. Ed. Engl._ 46, 2257–2261 (2007). CAS  PubMed  Google Scholar  *


Greshock, T.J., Grubbs, A.W., Tsukamoto, S. & Williams, R.M. A concise, biomimetic total synthesis of stephacidin A and notoamide B. _Angew. Chem. Int. Ed. Engl._ 46, 2262–2265 (2007).


CAS  PubMed  Google Scholar  * Finefield, J.M. & Williams, R.M. Synthesis of notoamide J: a potentially pivotal intermediate in the biosynthesis of several prenylated indole alkaloids.


_J. Org. Chem._ 75, 2785–2789 (2010). CAS  PubMed  PubMed Central  Google Scholar  * Tsukamoto, S., Umaoka, H., Yoshikawa, K., Ikeda, T. & Hirota, H. Notoamide O, a structurally


unprecendented prenylated indole alkaloid, and notoamides P-R from a marine-derived fungus, _Aspergillus_ sp. _J. Nat. Prod._ 73, 1438–1440 (2010). CAS  PubMed  Google Scholar  * Tsukamoto,


S. et al. Notoamides F-K, prenylated indole alkaloids isolated from a marine-derived _Apergillus_ sp. _J. Nat. Prod._ 71, 2064–2067 (2008). CAS  PubMed  Google Scholar  * Ding, Y. et al.


Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived _Aspergillus_ sp. _J. Am. Chem. Soc._ 132,


12733–12740 (2010). CAS  PubMed  PubMed Central  Google Scholar  * Artman, G.D. III, Grubbs, A.W. & Williams, R.M. Concise, asymmetric, stereocontrolled total synthesis of stephacidins


A, B and notoamide B. _J. Am. Chem. Soc._ 129, 6336–6342 (2007). CAS  PubMed  PubMed Central  Google Scholar  * Tsukamoto, S. et al. Isolation of notoamide E, a key precursor in the


biosynthesis of prenylated indole alkaloids in a marine-derived fungus, _Aspergillus_ sp. _J. Am. Chem. Soc._ 131, 3834–3835 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Greshock,


T.J. et al. Isolation, structure elucidation, and biomimetic total synthesis of versicolamide B, and the isolation of antipodal (−)-stephacidin A and (+)-notoamide B from _Aspergillus


versicolor_ NRRL 35600. _Angew. Chem. Int. Ed. Engl._ 47, 3573–3577 (2008). CAS  PubMed  PubMed Central  Google Scholar  * Tsukamoto, S. et al. Isolation of antipodal (−)-versicolamide B and


notoamide L-N from a marine-derived _Aspergillus_ sp. _Org. Lett._ 11, 1297–1300 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Williams, R.M. Natural product synthesis: Enabling


tools to penetrate Nature's secrets of biogenesis and biomechanism. _J. Org. Chem._ 76, 4221–4259 (2011). A REVIEW THAT SUMMARIZES THE BIOSYNTHETIC INVESTIGATIONS OF THE PRENYLATED


ALKALOIDS, HIGHLIGHTING UNEXPECTED DISCOVERIES AND DEVELOPMENT OF SYNTHETIC TECHNOLOGIES. CAS  PubMed  PubMed Central  Google Scholar  * Kelly, W.L. Intramolecular cyclizations of polyketide


biosynthesis: mining for a “Diels-Alderase”? _Org. Biomol. Chem._ 6, 4483–4493 (2008). CAS  PubMed  Google Scholar  * Pohnert, G. Macrophomate synthase: the first structure of a natural


Diels-Alderase. _ChemBioChem_ 4, 713–715 (2003). CAS  PubMed  Google Scholar  * Stocking, E.M. & Williams, R.M. Chemistry and biology of biosynthetic Diels-Alder reactions. _Angew. Chem.


Int. Ed. Engl._ 42, 3078–3115 (2003). CAS  PubMed  Google Scholar  * Kim, H.J., Ruszczycky, M.W., Choi, S., Liu, Y. & Liu, H. Enzyme-catalysed [4+2] cycloaddition is a key step in the


biosynthesis of spinosyn A. _Nature_ 473, 109–112 (2011). THE FIRST REPORT OF AN ENZYME THAT EXCLUSIVELY CATALYZES A DIELS-ALDER REACTION. CAS  PubMed  PubMed Central  Google Scholar  *


Campbell, C.D. & Vederas, J.C. Biosynthesis of lovastatin and related metabolites formed by fungal iterative PKS enzymes. _Biopolymers_ 93, 755–763 (2010). CAS  PubMed  Google Scholar  *


Brastianos, H.C. et al. Exiguamine A, an indole-2,3-dioxygenase (IDO) ihibitor isolated from the marine sponge _Neopetrosia exigua_. _J. Am. Chem. Soc._ 128, 16046–16047 (2006). CAS  PubMed


  Google Scholar  * Löb, S., Königsrainer, A., Rammensee, H.-G., Opelz, G. & Terness, P. Inhibitors of indoleamine-2,3-dioxygenase for cancer therapy: can we see the wood for the trees?


_Nat. Rev. Cancer_ 9, 445–452 (2009). PubMed  Google Scholar  * Volgraf, M. et al. Biomimetic synthesis of the IDO inhibitors exiguamine A and B. _Nat. Chem. Biol._ 4, 535–537 (2008). A


REPORT ON THE BIOMIMETIC SYNTHESIS OF EXIGUAMINE A AND DISCOVERY OF EXIGUAMINE B, WHICH ALSO EXAMINES THE POSSIBLE BIOSYNTHETIC LINKS BETWEEN THE TWO CONGENERS. CAS  PubMed  Google Scholar 


* O'Malley, D.P., Li, K., Maue, M., Zografos, A.L. & Baran, P.S. Total synthesis of dimerica pyrrole-imidazole alkaloids: Sceptrin, ageliferin, nagelamide E, oxysceptrin, nakamuric


acid, and the axinellamine carbon skeleton. _J. Am. Chem. Soc._ 129, 4762–4775 (2007). CAS  PubMed  Google Scholar  * Walker, R.P., Faulkner, D.J., Van Engen, D. & Clardy, J. Sceptrin,


an antimicrobial agent from the sponge _Agelas sceptrum_. _J. Am. Chem. Soc._ 103, 6772–6773 (1981). CAS  Google Scholar  * Kinnel, R.B., Gehrken, H.-P. & Scheuer, P.J. Palau'amine:


a cytotoxic and immunosuppressive hexacyclic bisguanidine antibiotic from the sponge _Stylotella agminata_. _J. Am. Chem. Soc._ 115, 3376–3377 (1993). CAS  Google Scholar  * Kinnel, R.B.,


Gehrken, H.-P., Swali, R., Skoropowski, G. & Scheuer, P.J. Palau'amine and its congeners: a family of bioactive bisguanidnes from the marine sponge _Stylotella aurantium_. _J. Org.


Chem._ 63, 3281–3286 (1998). CAS  Google Scholar  * Kato, T., Shizuri, Y., Izumida, H., Yokoyama, A. & Endo, M. Styloguanidines, new chitinase inhibitors from the marine _Stylotella


aurantium_. _Tetrahedr. Lett._ 36, 2133–2136 (1995). CAS  Google Scholar  * Kobayashi, J., Suzuki, M. & Tsuda, M. Konbu'acidin A, a new bromopyrrole alkaloid with cdk4 inhibitory


activity from _Hymeniacidon_ sponge. _Tetrahedron_ 53, 15681–15684 (1997). CAS  Google Scholar  * Kobayashi, H. et al. Carteramine A, an inhibitor of neutrophil chemotaxis, from the marine


sponge _Stylissa carteri_. _Tetrahedr. Lett._ 48, 2127–2129 (2007). CAS  Google Scholar  * Buchanan, M.S. et al. Natural products, stylissadines A and B, specific antagonists of the P2X7


receptor, and important inflammatory target. _J. Org. Chem._ 72, 2309–2317 (2007). CAS  PubMed  Google Scholar  * Buchanan, M.S., Carroll, A.R. & Quinn, R.J. Revised structure of


palau'amine. _Tetrahedr. Lett._ 48, 4573–4574 (2007). CAS  Google Scholar  * Grube, A. & Köck, M. Structural assignment of tetrabromostyloguanidine: does the relative configuration


of the palau'amines need revision? _Angew. Chem. Int. Ed. Engl._ 46, 2320–2324 (2007). CAS  PubMed  Google Scholar  * Lanman, B.A., Overman, L.E., Paulini, R. & White, N.S. On the


structure of palau'amine: evidence for the revised relative configuration from chemical synthesis. _J. Am. Chem. Soc._ 129, 12896–12900 (2007). CAS  PubMed  PubMed Central  Google


Scholar  * Seiple, I.B. et al. Total synthesis of Palau'amine. _Angew. Chem. Int. Ed. Engl._ 49, 1095–1098 (2010). THE FIRST REPORTED TOTAL SYNTHESIS OF THE PYRROLE-IMIDZAOLE ALKALOID


PALAU'AMINE, CORROBORATING THE PREVIOUSLY REPORTED STRUCTURE REVISION. CAS  PubMed  PubMed Central  Google Scholar  * Al Mourabit, A. & Potier, P. Sponge's molecular diversity


through the ambivalent reactivity of 2-aminoimidazole: a universal chemical pathway to the oroidin-based pyrrole-imidazole alkaloids and their palau'amine congeners. _European J. Org.


Chem._ 237–243 (2001). * Hoffmann, H. & Lindel, T. Synthesis of the pyrrole-imidazole alkaloids. _Synthesis_ 2003, 1753–1783 (2003). Google Scholar  * Jacquot, D.E.N. & Lindel, T.


Challenge palau'amine: current standings. _Curr. Org. Chem._ 9, 1551–1565 (2005). CAS  Google Scholar  * Weinreb, S.M. Some recent advances in the synthesis of polycyclic


imidazole-containing marine natural products. _Nat. Prod. Rep._ 24, 931–948 (2007). CAS  PubMed  Google Scholar  * Ma, Z., Lu, J., Wang, X. & Chen, C. Revisiting the Kinnel-Scheuer


hypothesis for the biosynthesis of palau'amine. _Chem. Commun. (Camb.)_ 47, 427–429 (2011). CAS  Google Scholar  * Kobayashi, J. et al. Ageliferins, potent actomyosin ATPase activators


from the Okinawan marine sponge _Agelas_ sp. _Tetrahedron_ 46, 5579–5586 (1990). CAS  Google Scholar  * Baran, P.S., O'Malley, D.P. & Zografos, A.L. Sceptrin as a potential


biosynthetic precursor to complex pyrrole-imidazole alkaloids: the total synthesis of ageliferin. _Angew. Chem. Int. Ed. Engl._ 43, 2674–2677 (2004). CAS  PubMed  Google Scholar  * Northrop,


B.H., O'Malley, D.P., Zografos, A.L., Baran, P.S. & Houk, K.N. Mechanism of the vinylcyclobutane rearrangement of sceptrin to ageliferin and nagelamide E. _Angew. Chem. Int. Ed.


Engl._ 45, 4126–4130 (2006). CAS  PubMed  Google Scholar  * Snyder, S.A., Zografos, A.L. & Lin, Y. Total synthesis of resveratrol-based natural products: a chemoselective solution.


_Angew. Chem. Int. Ed. Engl._ 46, 8186–8191 (2007). A REPORT DISCUSSING THE USE OF TRICYCLIC SYNTHONS FOR THE SYNTHESIS OF SEVERAL OLIGOMERIC RESVERATROL NATURAL PRODUCTS. CAS  PubMed 


Google Scholar  * Snyder, S.A., Breazzano, S.P., Ross, A.G., Lin, Y. & Zografos, A.L. Total synthesis of diverse carbogenic complexity within the resvertrol class from a common building


block. _J. Am. Chem. Soc._ 131, 1753–1765 (2009). CAS  PubMed  Google Scholar  * Stierle, A.A., Stierle, D.B. & Kelly, K. Berkelic acid, a novel spiroketal with selective anticancer


activity from an acid mine waste fungal extremophile. _J. Org. Chem._ 71, 5357–5360 (2006). CAS  PubMed  Google Scholar  * Buchgraber, P. et al. A synthesis-driven strcuture revision of


berkelic acid methyl ester. _Angew. Chem. Int. Ed. Engl._ 47, 8450–8454 (2008). CAS  PubMed  Google Scholar  * Wu, X., Zhou, J. & Snider, B.B. Synthesis of (−)-berkelic acid. _Angew.


Chem. Int. Ed._ 48, 1283–1286 (2009). CAS  Google Scholar  * Bender, C.F., Yoshimoto, F.K., Paradise, C.L. & De Brabander, J.K. A concise synthesis of berkelic acid insprired by


combining the natural products spicifernin and pulvilloric acid. _J. Am. Chem. Soc._ 131, 11350–11352 (2009). CAS  PubMed  PubMed Central  Google Scholar  * Liu, B. & De Brabander, J.K.


Metal-catalyzed regioselective oxy-functionlization of internal alkyne: an entry into ketones, acetals, and spiroketals. _Org. Lett._ 8, 4907–4910 (2006). CAS  PubMed  Google Scholar  * De


Brabander, J.K., Liu, B. & Au Qian, M. Au(I)- and Pt(II)-catalyzed cycloetherification of ω-hydroxy propargylic esters. _Org. Lett._ 10, 2533–2536 (2008). CAS  PubMed  Google Scholar  *


Dehn, R. et al. Molecular basis of elansolid biosynthesis: evidence for an unprecedented quinone methide initiated intramolecular Diels-Alder cycloaddition/macrolactonization. _Angew. Chem.


Int. Ed. Engl._ 50, 3882–3887 (2011). AN EXAMPLE OF A QUINONE METHIDE USED AS A SUBSTRATE FOR A DIELS-ALDER CYCLOADDITION REACTION IN NATURAL PRODUCT SYNTHESIS. CAS  PubMed  Google Scholar 


* Nakajima, H., Fujimoto, H., Matsumoto, R. & Hamasaki, T. Biosynthesis of spiciferone A and spicifernin, bioactive metabolites of the phytopathogenic fungus, _Cochliobolus spicifer_.


_J. Org. Chem._ 58, 4526–4528 (1993). CAS  Google Scholar  * Eschenmoser, A. Vitamin B12: Experiments concerning the origin of its molecular structure. _Angew. Chem. Int. Ed. Engl._ 27, 5–39


(1988). A REVIEW THAT DESCRIBES HOW THE TOTAL SYNTHESIS OF VITAMIN B12 SPURRED INVESTIGATIONS INTO ITS BIOSYNTHESIS AND THE ORIGIN OF THE CORRIN SUBSTRUCTURE. Google Scholar  Download


references ACKNOWLEDGEMENTS We thank J.M. Ready and U.K.Tambar (University of Texas Southwestern) for critical reading of this manuscript. We gratefully acknowledge financial support by the


National Institutes of Health (CA 90349) and the Robert A. Welch Foundation (I-1422). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biochemistry, The University of Texas


Southwestern Medical Center at Dallas, Dallas, Texas, USA Mina Razzak & Jef K De Brabander Authors * Mina Razzak View author publications You can also search for this author inPubMed 


Google Scholar * Jef K De Brabander View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Jef K De Brabander. ETHICS


DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Razzak, M., De


Brabander, J. Lessons and revelations from biomimetic syntheses. _Nat Chem Biol_ 7, 865–875 (2011). https://doi.org/10.1038/nchembio.709 Download citation * Published: 15 November 2011 *


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