Article
Chemistry, Multidisciplinary
Yuan Jin, Kensuke Orihara, Fumiki Kawagishi, Tatsuya Toma, Tohru Fukuyama, Satoshi Yokoshima
Summary: The total synthesis of Haliclonin A was achieved through a series of reactions including Birch reduction/alkylation, ring-closing metathesis, intramolecular cyclopropanation, and stereoselective 1,4-addition, leading to the formation of the desired compound.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Nicholas L. Magann, Mitchell T. Blyth, Michael S. Sherburn
Summary: The concise synthesis of alkaloid lythranidine utilizes the target's C-2 symmetry, adopting a two directional synthetic approach to efficiently access gram quantities of the natural product. The broad-spectrum nature of the synthesis is demonstrated through the preparation of three diastereomeric analogues of the natural product.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Chi He, Yu Wang, Cheng Bi, David S. Peters, Timothy J. Gallagher, Johannes Teske, Jason S. Chen, Rachel Corsetti, Anthony D'Onofrio, Kim Lewis, Phil S. Baran
Summary: A modular total synthesis method for kibdelomycin has been disclosed, which allows for structure-activity relationship studies. This method uses simple building blocks and addresses lingering questions regarding its structural assignment and its relationship to amycolamicin. Initial antibacterial assays indicate that both C-22 epimers of the natural product exhibit similar activity, while structurally truncated analogs lose activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Jun Shimura, Yoshio Ando, Ken Ohmori, Keisuke Suzuki
Summary: The first total synthesis of saptomycin H is reported in this study, which allows the determination of the unidentified absolute stereochemistry of the oxiranyl side chain as 14R,16S. The key steps include the concise assembly of three units (anthrone, sugar, and side chain) and the AZADOL-mediated 6-endo-selective pyranone formation.
Article
Chemistry, Multidisciplinary
Lorenz E. Loeffler, Conny Wirtz, Alois Fuerstner
Summary: This paper presents a new approach to chemical synthesis that allows for the preparation of a variety of casbane derivatives, especially the more highly oxygenated and arguably more relevant members of the family. Key design elements include catalyst-controlled intramolecular cyclopropanation, chain extension of stereoisomeric cyclopropane building blocks, and ring-closing alkyne metathesis. The concise total syntheses of depressin, yuexiandajisu A, and ent-pekinenin C demonstrate the effectiveness of this method.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Shunya Takahashi, Takenori Hama, Toshihiko Nogawa, Narihito Ogawa, Hiroyuki Koshino
Summary: This paper discusses the total synthesis of clostrienose, a cellular differentiation regulator from Clostridium acetobutylicum. The synthesis involves stereoselective construction of a skipped-triene system in clostrienoic acid and its subsequent esterification with a disaccharide residue. The partially protected clostrienoic acid used for the coupling reaction is also employed for the preparation of L-rhamnosyl clostrienoate, providing unambiguous confirmation of the proposed structure.
Article
Chemistry, Multidisciplinary
Annie R. Hooper, Andraz Ostrek, Ana Milian-Lopez, David Sarlah
Summary: This study presents a chemical synthesis method for preparing pyritide A2, involving the synthesis of a pyridine ring from an amino acid precursor, resulting in the efficient preparation of this class of natural products and analogues.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Yosuke Nakata, Junhao Fu, Hiroaki Itoh, Suresh Panthee, Hiroshi Hamamoto, Kazuhisa Sekimizu, Masayuki Inoue
Summary: This study developed a method to synthesize five tryptophan isomers and applied them in solid-phase peptide synthesis. The substitution at position C3 was found to affect the structure and function of peptides and proteins. The synthesis of the five isomers was achieved through peptide elongation, resin-based macrocyclization, and global deprotection, and their reduced antibacterial activity highlighted the importance of the precise three-dimensional structure of tryptophan in lysocin E. This approach provides a new strategy for analyzing and modifying the specific functions of tryptophan-containing peptides and proteins.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Yassin M. Elbatrawi, Taylor Gerrein, Avraz Anwar, Kamlesh M. Makwana, David Degen, Richard H. Ebright, Juan R. Del Valle
Summary: We have achieved the total synthesis and configurational assignment of pargamicin A, a highly oxidized nonribosomal peptide that effectively inhibits the growth of drug-resistant bacteria. Our synthetic strategy involves late-stage piperazine ring formation and careful selection of condensation reagents to assemble the densely substituted hexapeptide backbone. This work facilitates the synthesis of pargamicin derivatives for structure-activity relationship studies and provides insights into accessing other piperazic acid-containing natural products with steric congestion.
Article
Chemistry, Multidisciplinary
Arnaldo X. Torres-Hernandez, Prathibha Desman, Thi Nguyen, Vinh Hoang, Yichao Zhang, Ashley Bartels, Ryan J. Rafferty
Summary: This report describes the first total synthesis of Balgacyclamide B using a 17-steps pathway and achieving a 2% overall yield. The synthetic pathway can be adapted for the synthesis of Balgacyclamide A and C. The importance of cyclization conditions in converting or retaining configuration of beta-hydroxy amides via dehydrative cyclization is emphasized. The synthetic pathway provides a new route for the recently isolated cyanobactin's and can be used to explore porin-mediated transportation in gram-negative bacteria.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Multidisciplinary Sciences
Kyan A. D'Angelo, Carly K. Schissel, Bradley L. Pentelute, Mohammad Movassaghi
Summary: The study presents a concise total synthesis method for himastatin, a natural product with an unusual homodimeric structure. The final-stage dimerization strategy used in the synthesis was inspired by a detailed understanding of the compound's biogenesis. By combining this approach with a modular synthesis, a series of designed derivatives of himastatin, including synthetic probes to investigate its antibiotic activity, were efficiently accessed.
Article
Chemistry, Multidisciplinary
Georg Spaeth, Alois Fuerstner
Summary: The introduction of aldgarose sugar to the C5-OH group of the macrocyclic aglycone of aldgamycin N is difficult. Hence, a revised synthesis route was used, and a new scalable method for the synthesis of this sugar was developed to reduce costs. The formation of the glycoside required mild conditions and allowed for late-stage functionalization of the macrolide ring.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Gontran Sangouard, Alessandro Zorzi, Yuteng Wu, Edouard Ehret, Mischa Schuettel, Sangram Kale, Cristina Diaz-Perlas, Jonathan Vesin, Julien Bortoli Chapalay, Gerardo Turcatti, Christian Heinis
Summary: The study introduces a novel strategy for synthesizing and screening combinatorial macrocyclic libraries on a picomolar scale using acoustic droplet ejection, reducing reaction volumes, reagent consumption, and synthesis time. This approach allows for the development of macrocycle ligands in a more efficient and scaled-down manner.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Yuichiro Kawamoto, Hideki Kitsukawa, Toyoharu Kobayashi, Hisanaka Ito
Summary: The enantioselective total synthesis of nesteretal A was accomplished in 15 steps through biomimetic cascade hemiacetalizations, along with other key features like Sharpless asymmetric dihydroxylation, diastereoselective 1,2-addition, Pd-catalyzed ene-type cyclization, and stereoselective epoxidation to construct a complex structure containing multiple quaternary carbons.
Article
Chemistry, Multidisciplinary
Moritz E. Hansen, Samuel O. Yasmin, Susanne Wolfrum, Erick M. Carreira
Summary: The first total syntheses of tricyclic mutanobactins A and B, lipopeptides incorporating a thiazepanone, isolated from Streptococcus mutans, a member of the human oral microbiome, were reported. These natural products were rapidly delivered through a cascade of cyclization reactions using a solid-phase peptide synthesis (SPPS) based route. This versatile process was also used for a streamlined synthesis of mutanobactin D. Additionally, an independent synthesis of a truncated mutanobactin A analog, utilizing a novel thiazepanone amino acid building block, was provided.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Julian M. Feilner, Franz-Lucas Haut, Thomas Magauer
Summary: Polyene cyclizations can produce molecular complexity in a single step, bifunctional polyenes utilize the unique reactivity of highly functionalized alkenes, and have the potential to synthesize complex polycycles.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Franz-Lucas Haut, Christoph Habiger, Lukas A. Wein, Klaus Wurst, Maren Podewitz, Thomas Magauer
Summary: A powerful method for the synthesis of tetrasubstituted furans has been developed, involving the regioselective ring-opening of 2,5-dihydrothiophenes followed by an oxidative cyclization. The potential for organic synthesis is highlighted by the total synthesis of bisabolene sesquiterpenoids using the obtained furans. Mechanistic experiments and computational studies revealed an unprecedented Pummerer-type rearrangement in the reaction process.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Raphael E. Wildermuth, Christian Steinborn, David M. Barber, Kim S. Muehlfenzl, Mario Kendlbacher, Peter Mayer, Klaus Wurst, Thomas Magauer
Summary: This study provides a thorough account of the evolution of the first total synthesis of (+)-cornexistin. Utilizing a chiral-pool strategy, the challenges of low yields and difficulties in stereocenter installation were successfully addressed. Key steps included an intermolecular NHK coupling, a syn-Evans-aldol reaction, an intramolecular allylic alkylation, and a stepwise hydrolysis of a beta-keto nitrile.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Julian M. Feilner, Immanuel Plangger, Klaus Wurst, Thomas Magauer
Summary: This study utilized highly functionalized bifunctional alkenes to achieve a polyene tetracyclization, leading to the total synthesis of the tricyclic diterpenoid pimara-15-en-3 alpha-8 alpha-diol. The versatile route also allowed for the preparation of a diverse library of cyclization precursors for the total synthesis of the tetracyclic nor-diterpenoid norflickinflimiod C, providing insights into complex pentacyclic products.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Editorial Material
Chemistry, Medicinal
Alessio Ciulli, Lawrence Hamann, Wolfgang Jahnke, Amit S. Kalgutkar, Thomas Magauer, Tobias Ritter, Vicky Steadman, Scott D. Williams, Georg Winter, Klemens Hoegenauer, Karl Heinz Krawinkler, Antonia F. Stepan
Summary: This report summarizes the key events and presentations given at the second biannual Alpine Winter Conference, which took place in January 2020 in St. Anton, Austria. With roughly 180 attendees from around the globe, this mid-sized conference provided a conducive environment for networking and exchanging ideas.
Article
Chemistry, Multidisciplinary
Franz-Lucas Haut, Niklas J. Feichtinger, Immanuel Plangger, Lukas A. Wein, Mira Mueller, Tim-Niclas Streit, Klaus Wurst, Maren Podewitz, Thomas Magauer
Summary: This study presents a new synthetic approach to polysubstituted pyrroles using 2,5-dihydrothiophenes, with the ring-opening of the heterocycle providing access to a panel of 1,3-dienes that undergo pyrrole formation in the presence of inexpensive chloramine-T trihydrate. The reaction is conducted in an open flask at ambient temperatures and key intermediates can be isolated by carefully adjusting the electronics and sterics of the 1,3-diene precursor. DFT studies identified a reaction mechanism involving a 6 pi-electrocyclization of a sulfilimine intermediate followed by spontaneous ring-contraction to reveal the pyrrole skeleton.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Kevin Rafael Sokol, Thomas Magauer
Summary: This review provides an overview of synthetic methods and strategies for constructing oxepin and dihydrooxepin motifs in the context of natural product synthesis, highlighting key steps of each example.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Multidisciplinary
Lukas Anton Wein, Klaus Wurst, Thomas Magauer
Summary: The study presented the construction of seven novel ent-trachylobane diterpenoids using a bioinspired synthetic strategy. Enantioselective and scalable access to five ent-trachylobanes was achieved in the first phase, with one compound produced on a 300 mg scale. Chemical C-H oxidation methods were then used in the second phase to selectively convert two higher functionalized ent-trachylobanes, revealing the potential and limitations of established protocols for complex molecule synthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Pharmacology & Pharmacy
Marion Maier, Stefan Olthoff, Kerstin Hill, Carolin Zosel, Thomas Magauer, Lukas Anton Wein, Michael Schaefer
Summary: The selective TRPV3 activator KS0365 increases intracellular calcium levels and accelerates migration of keratinocytes, potentially promoting re-epithelialization upon skin wounding.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Jan Paciorek, Denis Hoefler, Kevin Rafael Sokol, Klaus Wurst, Thomas Magauer
Summary: A general synthetic approach to dihydrooxepine-spiroisoxazoline (DOSI) natural products was reported, leading to the first racemic total synthesis of psammaplysin A. The synthesis strategy involved two key transformations: a diastereoselective Henry reaction/cyclization sequence for the hydroxylated isoxazoline scaffold and a regioselective Baeyer-Villiger ring expansion for the dihydrooxepine fragment. The overall synthesis required 13 steps and utilized inexpensive starting materials.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Immanuel Plangger, Klaus Wurst, Thomas Magauer
Summary: We have achieved the total synthesis of eight ent-pimaranes for the first time via a short and enantioselective route (11-16 steps). Key features of this divergent synthesis include Sharpless asymmetric dihydroxylation, Bronsted acid catalyzed cationic bicyclization, and mild Rh-catalyzed arene hydrogenation, enabling rapid access to a late synthetic branching point. Selective functional group manipulations further allow for the synthesis of ent-pimaranes with different modifications in the A- and C-rings.
Article
Chemistry, Multidisciplinary
Immanuel Plangger, Tobias Pinkert, Klaus Wurst, Thomas Magauer
Summary: We have developed a concise asymmetric total synthesis method to access nine sesquiterpenoid alkaloids with four different tetra-/pentacyclic scaffolds in 5-8 steps. The key step of this synthesis is a bioinspired indole N-terminated cationic tricyclization, which enables the divergent synthesis of greenwayodendrines and polysin. By varying the precursor for the C2-substituted indole cyclization, the indole N- and C-termination can be switched, leading to the synthesis of greenwaylactams and polyveoline.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Christian Steinborn, Aldo Tancredi, Christoph Habiger, Christina Diederich, Jan Kramer, Anna M. Reingruber, Bernd Laber, Joerg Freigang, Gudrun Lange, Dirk Schmutzler, Anu Machettira, Gilbert Besong, Thomas Magauer, David M. Barber
Summary: We designed and synthesized simplified analogues of the herbicidal natural product (+)-cornexistin and evaluated their biological activity. Based on the X-Ray co-crystal structure of cornexistin bound to transketolase from Zea mays, we investigated the key interactions necessary for cornexistin's herbicidal profile. Three novel analogues were prepared, and the importance of substituents on the nine-membered ring of cornexistin was investigated. One analogue maintained a good level of biological activity and could provide insights for further optimization of cornexistin's structure in future commercialization.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Christian Steinborn, Tatjana Huber, Julian Lichtenegger, Immanuel Plangger, Klaus Wurst, Thomas Magauer
Summary: The first asymmetric total synthesis of waixenicinA, a potent TRPM7 inhibitor, was achieved. The synthesis involved the construction of a characteristic trans-fused oxabicyclo[7.4.0]-tridecane ring system through a diastereoselective conjugate addition/trapping sequence, followed by an intramolecular alkylation to form a 9-membered ring. The synthesis also employed a beta-keto sulfone motif for efficient ring-closure and a fluoride-mediated decarboxylation to prevent isomerization. Additionally, a base-mediated rearrangement reaction led to the synthesis of xeniafaraunol A.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Christian Steinborn, Tatjana Huber, Julian Lichtenegger, Immanuel Plangger, Denis Hoefler, Simon D. Schnell, Lara Weisheit, Peter Mayer, Klaus Wurst, Thomas Magauer
Summary: This article presents the efforts made to synthesize waixenicin A, with multiple strategies attempted before a successful synthesis was achieved.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
