Bio


Assistant Professor Noah Burns’ research explores the boundaries of modern organic synthesis to more rapidly create species of the highest molecular complexity. Projects in the Burns Lab take particular inspiration from natural products, not only for their importance as synthetic targets, but also for their potential to identify important unanswered scientific questions.

Noah Burns was born in Oakland, California, but grew up in south central Maine. He studied chemistry at Columbia University (B.A. 2004 summa cum laude), under the mentorship of Professor James Leighton. His doctoral work with Professor Phil Baran at the Scripps Research Institute in La Jolla, California (Ph.D. 2009) addressed the synthesis of haouamine A, a marine alkaloid. He then developed a catalytic enantioselective [5+2] cycloaddition as an NIH postdoctoral fellow with Professor Eric Jacobsen at Harvard University. He joined the Stanford Chemistry Department faculty in 2012, and was named a Terman Fellow in 2013.

Today, the Burns Lab focuses major efforts on the selective halogenation of organic molecules. Dihalogenation and halofunctionalization encompass some of the most fundamental transformations in our field, yet methods capable of accessing relevant halogenated motifs in a chemo-, regio-, and enantioselective fashion are lacking. Breakthroughs in this area could enable the controlled evaluation of the therapeutic potential of numerous chiral organohalogens.

The group also explores the practical total synthesis of natural products where there is true impetus for their construction due to unanswered chemical, medicinal, biological, and/or biophysical questions. Lab members are specifically engaged in the construction of unusual lipids with intriguing physical properties, for which synthesis offers a unique opportunity for study.

Academic Appointments


Administrative Appointments


  • Faculty Mentor, Stanford ChemH CBI Training Program (2014 - Present)

Honors & Awards


  • Amgen Young Investigator Award, Amgen (2017)
  • Dean's Award for First Years of Teaching, Stanford University (2016-2017)
  • Terman Fellow, Stanford University (2013-2016)
  • Thieme Chemistry Journal Award, Thieme Chemistry (2012)
  • NRSA Postdoctoral Fellowship, NIH (2009-2011)
  • Foundation Scholarship, ARCS Foundation (2006-2008)
  • Excellence in Chemistry Award, Roche (2006)
  • Dean’s Fellowship, TSRI (2005-2006)
  • Summa Cum Laude, Columbia University (2004)
  • Phi Beta Kappa, Phi Beta Kappa Society (2004)
  • Barry M. Goldwater Scholarship, Barry Goldwater Scholarship and Excellence in Education Program (2003)

Professional Education


  • Postdoctoral Fellow (NIH), Harvard University, Enantioselective catalysis (2012)
  • Doctor of Philosophy, The Scripps Research Institute, Natural product total synthesis (2009)
  • Bachelor of Arts, Columbia University, Chemistry (2004)

Current Research and Scholarly Interests


Research in our group explores the boundaries of modern organic synthesis to enable the more rapid creation of the highest molecular complexity in a predictable and controllable fashion. We are particularly inspired by natural products not only because of their importance as synthetic targets but also due to their ability to serve as invaluable identifiers of unanswered scientific questions.

One major focus of our research is selective halogenation of organic molecules. Dihalogenation and halofunctionalization encompass some of the most fundamental transformations in our field, yet methods capable of accessing relevant halogenated motifs in a chemo-, regio-, and enantioselective fashion are lacking.

We are also interested in the practical total synthesis of natural products for which there is true impetus for their construction due to unanswered chemical, medicinal, biological, or biophysical questions. We are specifically engaged in the construction of unusual lipids with unanswered questions regarding their physical properties and for which synthesis offers a unique opportunity for study.

2019-20 Courses


Stanford Advisees


All Publications


  • Enantioselective Synthesis of Azamerone JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Landry, M. L., McKenna, G. M., Burns, N. Z. 2019; 141 (7): 2867–71
  • Enantioselective Synthesis of Azamerone. Journal of the American Chemical Society Landry, M. L., McKenna, G. M., Burns, N. Z. 2019

    Abstract

    A concise and selective synthesis of the dichlorinated meroterpenoid azamerone is described. The paucity of tactics for the synthesis of natural-product-relevant chiral organochlorides motivated the development of unique strategies for accessing these motifs in enantioenriched forms. The route features a novel enantioselective chloroetherification reaction, a Pd-catalyzed cross-coupling between a quinone diazide and a boronic hemiester, and a late-stage tetrazine [4+2]-cycloaddition/oxidation cascade.

    View details for PubMedID 30707836

  • Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space ACS CENTRAL SCIENCE Kearney, S. E., Zahoranszky-Kohalmi, G., Brimacombe, K. R., Henderson, M. J., Lynch, C., Zhao, T., Wan, K. K., Itkin, Z., Dillon, C., Shen, M., Cheff, D. M., Lee, T. D., Bougie, D., Cheng, K., Coussens, N. P., Dorjsuren, D., Eastman, R. T., Huang, R., Iannotti, M. J., Karavadhi, S., Klumpp-Thomas, C., Roth, J. S., Sakamuru, S., Sun, W., Titus, S. A., Yasgar, A., Zhang, Y., Zhao, J., Andrade, R. B., Brown, M., Burns, N. Z., Cha, J. K., Mevers, E. E., Clardy, J., Clement, J. A., Crooks, P. A., Cuny, G. D., Ganor, J., Moreno, J., Morrill, L. A., Picazo, E., Susick, R. B., Garg, N. K., Goess, B. C., Grossman, R. B., Hughes, C. C., Johnston, J. N., Joullie, M. M., Kinghorn, A., Kingston, D. I., Krische, M. J., Kwon, O., Maimone, T. J., Majumdar, S., Maloney, K. N., Mohamed, E., Murphy, B. T., Nagorny, P., Olson, D. E., Overman, L. E., Brown, L. E., Snyder, J. K., Porco, J. A., Rivas, F., Ross, S. A., Sarpong, R., Sharma, I., Shaw, J. T., Xu, Z., Shen, B., Shi, W., Stephenson, C. J., Verano, A. L., Tan, D. S., Tang, Y., Taylor, R. E., Thomson, R. J., Vosburg, D. A., Wu, J., Wuest, W. M., Zakarian, A., Zhang, Y., Ren, T., Zuo, Z., Inglese, J., Michael, S., Simeonov, A., Zheng, W., Shinn, P., Jadhav, A., Boxer, M. B., Hall, M. D., Xia, M., Guha, R., Rohde, J. M. 2018; 4 (12): 1727–41
  • Catalytic Regio- and Enantioselective Haloazidation of Allylic Alcohols. Journal of the American Chemical Society Seidl, F. J., Min, C., Lopez, J. A., Burns, N. Z. 2018

    Abstract

    Herein we report a highly regio- and stereoselective haloazidation of allylic alcohols. This enantioselective reaction uses readily available materials and can be performed on a variety of alkyl-substituted alkenes and can incorporate either bromine or chlorine as the electrophilic halogen component. Both halide and azido groups of the resulting products can be transformed into valuable building blocks with complete stereospecificity. The first example of an enantioselective 1,4-haloazidation of a conjugated diene is reported as well as its application to a concise synthesis of an aza-sugar.

    View details for PubMedID 30403852

  • Synthesis and Mechanochemical Activation of Ladderene-Norbornene Block Copolymers. Journal of the American Chemical Society Su, J. K., Feist, J. D., Yang, J., Mercer, J. A., Romaniuk, J. A., Chen, Z., Cegelski, L., Burns, N. Z., Xia, Y. 2018; 140 (39): 12388–91

    Abstract

    We have recently reported a polymechanophore system, polyladderene (PLDE), which dramatically transforms into polyacetylene (PA) upon mechanical stimulation. Herein, we optimized conditions to synthesize unprecedented block copolymers (BCPs) containing a force-responsive block by sequential ring-opening metathesis polymerization of different norbornenes and bromoladderene. Successful extension from PLDE to other blocks required careful timing and low temperatures to preserve the reactivity of the PLDE-appended catalyst. The PLDE-containing BCPs were sonochemically activated into visually soluble PA with a maximum absorption lambda ≥ 600 nm and unique absorption patterns corresponding to noncontinuous activation of ladderene units. Access to polymechanophore BCPs paves the way for new stress-responsive materials with solution and solid state self-assembly behaviors and incorporation of polymechanophores into other materials.

    View details for PubMedID 30229652

  • Ladderane phospholipids form a densely packed membrane with normal hydrazine and anomalously low proton/hydroxide permeability. Proceedings of the National Academy of Sciences of the United States of America Moss, F. R., Shuken, S. R., Mercer, J. A., Cohen, C. M., Weiss, T. M., Boxer, S. G., Burns, N. Z. 2018

    Abstract

    Ladderane lipids are unique to anaerobic ammonium-oxidizing (anammox) bacteria and are enriched in the membrane of the anammoxosome, an organelle thought to compartmentalize the anammox process, which involves the toxic intermediate hydrazine (N2H4). Due to the slow growth rate of anammox bacteria and difficulty of isolating pure ladderane lipids, experimental evidence of the biological function of ladderanes is lacking. We have synthesized two natural and one unnatural ladderane phosphatidylcholine lipids and compared their thermotropic properties in self-assembled bilayers to distinguish between [3]- and [5]-ladderane function. We developed a hydrazine transmembrane diffusion assay using a water-soluble derivative of a hydrazine sensor and determined that ladderane membranes are as permeable to hydrazine as straight-chain lipid bilayers. However, pH equilibration across ladderane membranes occurs 5-10 times more slowly than across straight-chain lipid membranes. Langmuir monolayer analysis and the rates of fluorescence recovery after photobleaching suggest that dense ladderane packing may preclude formation of proton/hydroxide-conducting water wires. These data support the hypothesis that ladderanes prevent the breakdown of the proton motive force rather than blocking hydrazine transmembrane diffusion in anammox bacteria.

    View details for PubMedID 30150407

  • Synthesis and study of noncanonical membrane lipids Burns, N. AMER CHEMICAL SOC. 2018
  • Ladderane phospholipids form dense, low-polarity membranes with low proton/hydroxide permeability Moss, F., Shuken, S., Mercer, J., Cohen, C., Weiss, T., Burns, N., Boxer, S. AMER CHEMICAL SOC. 2018
  • Catalytic Enantioselective Dihalogenation in Total Synthesis ACCOUNTS OF CHEMICAL RESEARCH Landry, M. L., Burns, N. Z. 2018; 51 (5): 1260–71

    Abstract

    To date, more than 5000 biogenic halogenated molecules have been characterized. This number continues to increase as chemists explore chloride- and bromide-rich marine environments in search of novel bioactive natural products. Naturally occurring organohalogens span nearly all biosynthetic structural classes, exhibit a range of unique biological activities, and have been the subject of numerous investigations. Despite the abundance of and interest in halogenated molecules, enantioselective methods capable of forging carbon-halogen bonds in synthetically relevant contexts remain scarce. Accordingly, syntheses of organohalogens often rely on multistep functional group interconversions to establish carbon-halogen stereocenters. Our group has developed an enantioselective dihalogenation reaction and utilized it in the only reported examples of catalytic enantioselective halogenation in natural product synthesis. In this Account, we describe our laboratory's development of a method for catalytic, enantioselective dihalogenation and the application of this method to the synthesis of both mono- and polyhalogenated natural products. In the first part, we describe the initial discovery of a TADDOL-mediated dibromination of cinnamyl alcohols. Extension of this reaction to a second-generation system capable of selective bromochlorination, dichlorination, and dibromination is then detailed. This system is capable of controlling the enantioselectivity of dihalide formation, chemoselectivity for polyolefinic substrates, and regioselectivity in the case of bromochlorination. The ability of this method to exert control over regioselectivity of halide delivery permits selective halogenation of electronically nonbiased olefins required for total synthesis. In the second part, we demonstrate how the described dihalogenation has provided efficient access to a host of structurally diverse natural products. The most direct application of this methodology is in the synthesis of naturally occurring vicinal dihalides. Chiral vicinal bromochlorides represent a class of >175 natural products; syntheses of five members of this class, including its flagship member, (+)-halomon, have been accomplished through use of the catalytic, enantioselective bromochlorination. Likewise, enantioselective dichlorination has provided selective access to two members of the chlorosulfolipids, a class of linear, acyclic polychlorides. Synthesis of chiral monohalides has been achieved through solvolysis of enantioenriched bromochlorides; this approach has resulted in the synthesis of five bromocyclohexane-containing natural products through an enantiospecific bromopolyene cyclization. In reviewing these syntheses, a framework for the synthesis of chiral organohalogens mediated by catalytic, enantioselective dihalogenation has emerged. The development of a selective dihalogenation method has been highly enabling in the synthesis of halogenated natural products. In this Account, we detail all examples of catalytic, enantioselective halogenation in total synthesis and encourage the further development of synthetically useful halogenation methodologies.

    View details for PubMedID 29664281

    View details for PubMedCentralID PMC5987034

  • Synthesis and Biophysical Characterization of the Chlorosulfolipids of Ochramonas danica McKenna, G. M., Moss, F. R., Landry, M. L., Burns, N. Z., Boxer, S. G. CELL PRESS. 2018: 16A
  • Ladderane Phospholipids Form Dense Membranes with Low Proton Permeability Moss, F. R., Shuken, S. R., Mercer, J. M., Cohen, C. M., Burns, N. Z., Boxer, S. G. CELL PRESS. 2018: 260A
  • Site-selective bromination of sp3 C-H bonds. Chemical science Sathyamoorthi, S., Banerjee, S., Du Bois, J., Burns, N. Z., Zare, R. N. 2018; 9 (1): 100–104

    Abstract

    A method for converting sp3 C-H to C-Br bonds using an N-methyl sulfamate directing group is described. The reaction employs Rh2(oct)4 and a mixture of NaBr and NaOCl and is performed in aqueous solution open to air. For all sulfamates examined, oxidation occurs with high selectivity at the γ-carbon, affording a uniquely predictable method for C-H bond halogenation. Results from a series of mechanistic experiments suggest that substrate oxidation likely proceeds by a radical chain process. Initial formation of an N-halogenated sulfamate followed by Rh-mediated homolysis generates an N-centered radical, which serves as the active oxidant.

    View details for PubMedID 29629078

  • Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space. ACS central science Kearney, S. E., Zahoránszky-Kőhalmi, G., Brimacombe, K. R., Henderson, M. J., Lynch, C., Zhao, T., Wan, K. K., Itkin, Z., Dillon, C., Shen, M., Cheff, D. M., Lee, T. D., Bougie, D., Cheng, K., Coussens, N. P., Dorjsuren, D., Eastman, R. T., Huang, R., Iannotti, M. J., Karavadhi, S., Klumpp-Thomas, C., Roth, J. S., Sakamuru, S., Sun, W., Titus, S. A., Yasgar, A., Zhang, Y. Q., Zhao, J., Andrade, R. B., Brown, M. K., Burns, N. Z., Cha, J. K., Mevers, E. E., Clardy, J., Clement, J. A., Crooks, P. A., Cuny, G. D., Ganor, J., Moreno, J., Morrill, L. A., Picazo, E., Susick, R. B., Garg, N. K., Goess, B. C., Grossman, R. B., Hughes, C. C., Johnston, J. N., Joullie, M. M., Kinghorn, A. D., Kingston, D. G., Krische, M. J., Kwon, O., Maimone, T. J., Majumdar, S., Maloney, K. N., Mohamed, E., Murphy, B. T., Nagorny, P., Olson, D. E., Overman, L. E., Brown, L. E., Snyder, J. K., Porco, J. A., Rivas, F., Ross, S. A., Sarpong, R., Sharma, I., Shaw, J. T., Xu, Z., Shen, B., Shi, W., Stephenson, C. R., Verano, A. L., Tan, D. S., Tang, Y., Taylor, R. E., Thomson, R. J., Vosburg, D. A., Wu, J., Wuest, W. M., Zakarian, A., Zhang, Y., Ren, T., Zuo, Z., Inglese, J., Michael, S., Simeonov, A., Zheng, W., Shinn, P., Jadhav, A., Boxer, M. B., Hall, M. D., Xia, M., Guha, R., Rohde, J. M. 2018; 4 (12): 1727–41

    Abstract

    Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (-)-2(S)-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening.

    View details for PubMedID 30648156

  • Site-selective bromination of sp3 C–H bonds Chem.Sci Sathyamoorthi, S., Banerjee, S., Du Bois, J., Burns, N. Z., Zare, R. N. 2018; 9: 100-104

    Abstract

    A method for converting sp3 C-H to C-Br bonds using an N-methyl sulfamate directing group is described. The reaction employs Rh2(oct)4 and a mixture of NaBr and NaOCl and is performed in aqueous solution open to air. For all sulfamates examined, oxidation occurs with high selectivity at the γ-carbon, affording a uniquely predictable method for C-H bond halogenation. Results from a series of mechanistic experiments suggest that substrate oxidation likely proceeds by a radical chain process. Initial formation of an N-halogenated sulfamate followed by Rh-mediated homolysis generates an N-centered radical, which serves as the active oxidant.

    View details for DOI 10.1039/C7SC04611A

    View details for PubMedCentralID PMC5873043

  • Enantiospecific Solvolytic Functionalization of Bromochlorides JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Burckle, A. J., Gal, B., Seidl, F. J., Vasilev, V. H., Burns, N. Z. 2017; 139 (38): 13562–69

    Abstract

    Herein, we report that under mild solvolytic conditions, enantioenriched bromochlorides can be ionized, stereospecifically cyclized to an array of complex bromocyclic scaffolds, or intermolecularly trapped by exogenous nucleophiles. Mechanistic investigations support an ionic mechanism wherein the bromochloride serves as an enantioenriched bromonium surrogate. Several natural product-relevant motifs are accessed in enantioenriched form for the first time with high levels of stereocontrol, and this technology is applied to the scalable synthesis of a polycyclic brominated natural product. Arrays of nucleophiles including olefins, alkynes, heterocycles, and epoxides are competent traps in the bromonium-induced cyclizations, leading to the formation of enantioenriched mono-, bi-, and tricyclic products. This strategy is further amenable to intermolecular coupling between cinnamyl bromochlorides and a diverse set of commercially available nucleophiles. Collectively, this work demonstrates that enantioenriched bromonium chlorides are configurationally stable under solvolytic conditions in the presence of a variety of functional groups.

    View details for PubMedID 28858493

  • Understanding the mechanochemistry of molecular ladders Chen, Z., Chen, L., Mercer, J., Zhu, X., Martinez, T., Burns, N., Xia, Y. AMER CHEMICAL SOC. 2017
  • Chemical synthesis and absolute stereochemical determination of a ladderane phospholipid Cohen, C., Burns, N. AMER CHEMICAL SOC. 2017
  • Mechanochemical unzipping of insulating polyladderene to semiconducting polyacetylene. Science (New York, N.Y.) Chen, Z., Mercer, J. A., Zhu, X., Romaniuk, J. A., Pfattner, R., Cegelski, L., Martinez, T. J., Burns, N. Z., Xia, Y. 2017; 357 (6350): 475–79

    Abstract

    Biological systems sense and respond to mechanical stimuli in a complex manner. In an effort to develop synthetic materials that transduce mechanical force into multifold changes in their intrinsic properties, we report on a mechanochemically responsive nonconjugated polymer that converts to a conjugated polymer via an extensive rearrangement of the macromolecular structure in response to force. Our design is based on the facile mechanochemical unzipping of polyladderene, a polymer inspired by a lipid natural product structure and prepared via direct metathesis polymerization. The resultant polyacetylene block copolymers exhibit long conjugation length and uniform trans-configuration and self-assemble into semiconducting nanowires. Calculations support a tandem unzipping mechanism of the ladderene units.

    View details for PubMedID 28774923

  • Chemical Synthesis and Self-Assembly of a Ladderane Phospholipid JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Mercer, J. A., Cohen, C. M., Shuken, S. R., Wagner, A. M., Smith, M. W., Moss, F. R., Smith, M. D., Vahala, R., Gonzalez-Martinez, A., Boxer, S. G., Burns, N. Z. 2016; 138 (49): 15845-15848

    Abstract

    Ladderane lipids produced by anammox bacteria constitute some of the most structurally fascinating yet poorly studied molecules among biological membrane lipids. Slow growth of the producing organism and the inherent difficulty of purifying complex lipid mixtures have prohibited isolation of useful amounts of natural ladderane lipids. We have devised a highly selective total synthesis of ladderane lipid tails and a full phosphatidylcholine to enable biophysical studies on chemically homogeneous samples of these molecules. Additionally, we report the first proof of absolute configuration of a natural ladderane.

    View details for DOI 10.1021/jacs.6b10706

    View details for Web of Science ID 000389962800013

    View details for PubMedID 27960308

    View details for PubMedCentralID PMC5279923

  • Chiral Alkyl Halides: Underexplored Motifs in Medicine MARINE DRUGS Gal, B., Bucher, C., Burns, N. Z. 2016; 14 (11)

    Abstract

    While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this review that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Our hope is that, by placing such compounds in the minds of the chemical community, they may gain more traction in drug discovery and inspire more synthetic chemists to develop methods for selective halogenation.

    View details for DOI 10.3390/md14110206

    View details for Web of Science ID 000390097800013

    View details for PubMedID 27827902

    View details for PubMedCentralID PMC5128749

  • A Unified Approach for the Enantioselective Synthesis of the Brominated Chamigrene Sesquiterpenes. Angewandte Chemie (International ed. in English) Burckle, A. J., Vasilev, V. H., Burns, N. Z. 2016; 55 (38): 11476-11479

    Abstract

    The brominated chamigrene sesquiterpenes constitute a large subclass of bromocyclohexane-containing natural products, yet no general enantioselective strategy for the synthesis of these small molecules exists. Herein we report a general strategy for accessing this family of secondary metabolites, including the enantioselective synthesis of (-)-α- and (-)-ent-β-bromochamigrene, (-)-dactylone, and (+)-aplydactone. Access to these molecules is enabled by a stereospecific bromopolyene cyclization initiated by the solvolysis of an enantiomerically enriched vicinal bromochloride.

    View details for DOI 10.1002/anie.201605722

    View details for PubMedID 27506430

  • Selective bromochlorination of a homoallylic alcohol for the total synthesis of (-)-anverene BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY Seidl, F. J., Burns, N. Z. 2016; 12: 1361-1365

    Abstract

    The scope of a recently reported method for the catalytic enantioselective bromochlorination of allylic alcohols is expanded to include a specific homoallylic alcohol. Critical factors for optimization of this reaction are highlighted. The utility of the product bromochloride is demonstrated by the first total synthesis of an antibacterial polyhalogenated monoterpene, (-)-anverene.

    View details for DOI 10.3762/bjoc.12.129

    View details for Web of Science ID 000379393800001

    View details for PubMedID 27559385

    View details for PubMedCentralID PMC4979643

  • Catalytic Enantioselective Dihalogenation and the Selective Synthesis of (-)-Deschloromytilipin A and (-)-Danicalipin A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Landry, M. L., Hu, D. X., McKenna, G. M., Burns, N. Z. 2016; 138 (15): 5150-5158

    Abstract

    A titanium-based catalytic enantioselective dichlorination of simple allylic alcohols is described. This dichlorination reaction provides stereoselective access to all common dichloroalcohol building blocks used in syntheses of chlorosulfolipid natural products. An enantioselective synthesis of ent-(-)-deschloromytilipin A and a concise, eight-step synthesis of ent-(-)-danicalipin A are executed and employ the dichlorination reaction as the first step. Extension of this system to enantioselective dibromination and its use in the synthesis of pentabromide stereoarrays relevant to bromosulfolipids is reported. The described dichlorination and dibromination reactions are capable of exerting diastereocontrol in complex settings allowing X-ray crystal structure analysis of natural and unnatural diastereomers of polyhalogenated stereohexads.

    View details for DOI 10.1021/jacs.6b01643

    View details for Web of Science ID 000374812100024

    View details for PubMedID 27018981

    View details for PubMedCentralID PMC4922634

  • Highly Selective Synthesis of Halomon, Plocamenone, and Isoplocamenone JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Bucher, C., Deans, R. M., Burns, N. Z. 2015; 137 (40): 12784-12787

    Abstract

    Over 160 chiral vicinal bromochlorinated natural products have been identified; however, a lack of synthetic methods for the selective incorporation of halogens into organic molecules has hindered their synthesis. Here we disclose the first total synthesis and structural confirmation of isoplocamenone and plocamenone, as well as the first selective and scalable synthesis of the preclinical anticancer natural product halomon. The synthesis of these inter-halogenated compounds has been enabled by our recently developed chemo-, regio-, and enantioselective dihalogenation reaction.

    View details for DOI 10.1021/jacs.5b08398

    View details for Web of Science ID 000363002900014

    View details for PubMedID 26394844

    View details for PubMedCentralID PMC4634703

  • Catalytic Chemo-, Regio-, and Enantioselective Bromochlorination of Allylic Alcohols JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Hu, D. X., Seidl, F. J., Bucher, C., Burns, N. Z. 2015; 137 (11): 3795-3798

    Abstract

    Herein we describe a highly chemo-, regio-, and enantioselective bromochlorination reaction of allylic alcohols, employing readily available halogen sources and a simple Schiff base as the chiral catalyst. The application of this interhalogenation reaction to a variety of substrates, the rapid enantioselective synthesis of a bromochlorinated natural product, and preliminary extension of this chemistry to dibromination and dichlorination are reported.

    View details for DOI 10.1021/jacs.5b01384

    View details for Web of Science ID 000351972000018

    View details for PubMedID 25738419

  • Natural products: Emulation illuminates biosynthesis. Nature chemistry Mercer, J. A., Burns, N. Z. 2015; 7 (11): 860–61

    View details for PubMedID 26492003

  • Catalytic enantioselective dibromination of allylic alcohols. Journal of the American Chemical Society Hu, D. X., Shibuya, G. M., Burns, N. Z. 2013; 135 (35): 12960-12963

    Abstract

    A new dibromination reaction involving the combination of dibromomalonate as the bromonium source and a titanium bromide species as the bromide source has been developed. Enantioselective catalysis has been achieved through apparent ligand acceleration by a tartaric acid-derived diol.

    View details for DOI 10.1021/ja4083182

    View details for PubMedID 23952929

  • ORGANIC CHEMISTRY Catalysis in tight spaces NATURE Burns, N. Z., Jacobsen, E. N. 2012; 483 (7389): 278-279

    View details for Web of Science ID 000301481800032

    View details for PubMedID 22422255

  • Mannich Reaction Science of Synthesis, Stereoselective Synthesis Z, B. N., N, J. E., G, D. J., A, M. G., Eds, E. A. 2011; 2 (785-834)
  • Dual Catalysis in Enantioselective OxidopyryliumBased [5+2] Cycloadditions J. Am. Chem. Soc Z, B. N., W, W. M., N, J. E. 2011; 133 (14578-14581)
  • Sulfhydryl-based dendritic chain reaction CHEMICAL COMMUNICATIONS Sella, E., Weinstain, R., Erez, R., Burns, N. Z., Baran, P. S., Shabat, D. 2010; 46 (35): 6575-6577

    Abstract

    A new dendritic chain reaction probe system was demonstrated to produce exponential signal amplification for the detection of sulfhydryl compounds.

    View details for DOI 10.1039/c0cc02195d

    View details for Web of Science ID 000281237600045

    View details for PubMedID 20714571

  • Scalable Total Synthesis and Biological Evaluation of Haouamine A and Its Atropisomer JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Burns, N. Z., Krylova, I. N., Hannoush, R. N., Baran, P. S. 2009; 131 (26): 9172-?

    Abstract

    A total synthesis of the complex, bent aromatic ring-containing marine alkaloid haouamine A is achieved through a route in which every step (with the exception of the final deprotection) is performed on a gram-scale. This is accomplished through the development of a method for the dehydrogenation of cyclohexenones that allows for point-to-planar chirality transfer. This strategy makes it possible to program the desired atropisomeric outcome from a simple chiral cyclohexenone. By synthesizing atrop-haouamine A, this work has firmly established that natural haouamine exists as a single, nonequilibrating atropisomer. Finally, biological investigations demonstrate that the bent aromatic ring of this natural product is critical for anticancer activity against PC3 cells.

    View details for DOI 10.1021/ja903745s

    View details for Web of Science ID 000267633300020

    View details for PubMedID 19530671

  • Redox Economy in Organic Synthesis ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Burns, N. Z., Baran, P. S., Hoffmann, R. W. 2009; 48 (16): 2854-2867

    Abstract

    "Economy" is referred to as the thrifty and efficient use of material resources, as the principle of "minimum effort to reach a goal." More illuminating is: "the aim to portion one's forces in order to use as little as possible of them to reach a goal." Such statements certainly apply when the goal is to synthesize a complex target molecule. Redox economy then implies the use of as few redox steps as possible in the synthetic conquest of a target compound. While any sort of economy will help to streamline the effort of total synthesis, redox economy addresses a particularly weak area in present-day total synthesis. It is not enough to point out the present deficiencies, rather the purpose of this Review is to serve as a teaching tool for all practitioners of the field by giving and illustrating guidelines to increase redox economy in multistep organic synthesis.

    View details for DOI 10.1002/anie.200806086

    View details for Web of Science ID 000265230900005

    View details for PubMedID 19294720

  • Total synthesis of Haouamine A: the IndenoTetrahydropyridine Core Tetrahedron Z, B. N., M, J., S, B. P. 2009; 65 (6600-6610)
  • On the origin of the haouamine alkaloids ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Burns, N. Z., Baran, P. S. 2008; 47 (1): 205-208

    View details for DOI 10.1002/anie.200704576

    View details for Web of Science ID 000251911400042

    View details for PubMedID 18038444

  • Total synthesis of (+/-)-haouamine A JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Baran, P. S., Burns, N. Z. 2006; 128 (12): 3908-3909

    Abstract

    The first total synthesis of the highly complex and potent anticancer agent haouamine A is reported through an eight-step sequence. Brevity of the sequence and complete control of chemo-, position-, and stereoselectivity (both planar and axial chirality) were possible through the invention of chemistry specifically tailored for the problems at hand, namely a cascade annulation proceeding via a hitherto unknown chemical entity for the indeno-tetrahydropyridine ring system as well as a pyrone-assisted stitching of the daunting bent-aromatic ring.

    View details for DOI 10.1021/ja0602997

    View details for Web of Science ID 000236401600030

    View details for PubMedID 16551088

  • The enantioselective allylation and crotylation of sterically hindered and functionalized aryl ketones: Convenient access to unusual tertiary carbinol structures ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Burns, N. Z., Hackman, B. M., Ng, P. Y., Powelson, I. A., Leighton, J. L. 2006; 45 (23): 3811-3813

    View details for DOI 10.1002/anie.200600910

    View details for Web of Science ID 000238335100016

    View details for PubMedID 16671141