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
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, Multidisciplinary
Feng-Yuan Wang, Lei Jiao
Summary: An asymmetric total synthesis of cage-like indole alkaloid arborisidine is achieved using a new synthetic strategy that involves a catalytic parallel kinetic resolution based on ambident nucleophilicity of indole and a 5-exo-trig radical cyclization.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Hao Yu, Zachary P. Sercel, Samir P. Rezgui, Jonathan Farhi, Scott C. Virgil, Brian M. Stoltz
Summary: This study describes a synthetic approach to aleutianamine and highlights its potent biological activity against human pancreatic cancer cells, making it a potential candidate for therapeutic development.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Vasil H. Vasilev, Lukas Spessert, Kuan Yu, Thomas J. Maimone
Summary: The large family of daphnane diterpene orthoesters (DDOs) represents a remarkable class of natural products both in terms of structure and function. They are potent lead compounds for the treatment of pain, neurodegeneration, HIV/AIDS, and cancer. However, the synthesis of DDO natural products remains rare.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Yang Wang, Yongjian Su, Yanxing Jia
Summary: In this research, the structurally intriguing diterpene (+)-aberrarone was synthesized in only 12 steps from commercially available (S,S)-carveol without protecting group manipulations. This concise synthesis includes a Cu-catalyzed asymmetric hydroboration to generate the chiral methyl group, a Ni-catalyzed reductive coupling to link two fragments, and a Mn-mediated radical cascade cyclization to construct the triquinane system.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Jiujian Ji, Jiajun Chen, Sixun Qin, Wanye Li, Jun Zhao, Guozhao Li, Hao Song, Xiao-Yu Liu, Yong Qin
Summary: This article reports the first total synthesis of vilmoraconitine using efficient ring-forming reactions. Key steps include an oxidative dearomatization-induced Diels-Alder cycloaddition, a hydrodealkenylative fragmentation/Mannich sequence, and an intramolecular Diels-Alder cycloaddition.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Stephan N. Hess, Xiaobin Mo, Conny Wirtz, Alois Fuerstner
Summary: Limaol, a marine-derived C40-polyketide, is unique in structure due to the nonthermodynamic array of four skipped methylene substituents on its hydrophobic tail. This distinctive segment was assembled using a two-directional approach and coupled to the polyether domain through an allyl/alkenyl Stille reaction under neutral conditions. The core region was prepared through several key steps, including asymmetric propargylation catalyzed by 3,3'-dibromo-BINOL, gold-catalyzed spirocyclization, and substrate-controlled allylation to introduce the southern sector.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Daria E. Kim, Yingchuan Zhu, Shingo Harada, Isaiah Aguilar, Abbigayle E. Cuomo, Minghao Wang, Timothy R. Newhouse
Summary: In this study, we successfully reported the total synthesis of the indole diterpenoid natural product shearilicine for the first time through an 11-step sequence using a generalizable precursor. The target molecule was obtained in an enantiospecific manner using a native chiral auxiliary strategy. The formation of the key carbazole substructure was achieved through a mild intramolecular Heck cyclization, which was promoted by noncovalent substrate-ligand and ligand-ligand interactions revealed by computational study.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Xianhuang Zeng, Dale L. Boger
Summary: The total synthesis of (-)-strempeliopine involves a powerful SmI2-mediated and BF3 center dot OEt2-initiated dearomative transannular radical cyclization onto an indole, resulting in the formation of a quaternary center and the strategic C19-C2 bond in its core structure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Sanghyeon Lee, Byung-Gyu Kim, Sujeong Geum, Jiheon Kim, Hee-Yoon Lee
Summary: The first total synthesis of (+/-)-jujuyane was achieved from a (5 + 3) dimerization product of oxidopyrylium ylide, which established the cyclooctanoid core structure with stereochemical bias. Selective functional group modifications of the dimeric structure, followed by strategic functional group manipulations around the eight-membered carbocyclic core, paved the way for the total synthesis of (+/-)-jujuyane and will guide future applications in natural product synthesis using oxidopyrylium dimers.
Article
Chemistry, Organic
Kazutoshi Tomoya, Kazuaki Komiya, Daisuke Nakajima, Nariyoshi Umekubo, Satoshi Yokoshima
Summary: A total synthesis of kopsone was achieved by stereoselective preparation of an acyclic aldehyde with a protected hydroxylamine moiety through Ireland-Claisen rearrangement and intramolecular cycloaddition of an eight-membered cyclic nitrone, forming the 2-azabicyclo[3.3.1]nonane skeleton.
Article
Chemistry, Organic
Xu-Kun Wang, Yue-Mei Jia, Yi-Xian Li, Chu-Yi Yu
Summary: A new antibiotic called pseudouridimycin with a unique mode of action against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains, was synthesized using an efficient and practical convergent strategy.
Article
Chemistry, Organic
Shiyuan Kang, Yinxia Wu, Min Hu, Ying Ma, Xiangdi Huang, Zhen Hao, Xiujuan Li, Wen Chen, Hongbin Zhang
Summary: The asymmetric total synthesis of vinorine, a complex cage-like alkaloid, has been achieved using a flexible approach. Key steps in this synthesis involve a rearrangement/cyclization reaction to form the functional 9-azabicyclo[3.3.1]nonane scaffold, a high yield indole annulation to create a common intermediate for sarpagine-ajamaline type alkaloids, and a rearrangement reaction to construct the C15-C20 bond.
Article
Chemistry, Organic
Shota Iiyama, Keisuke Fukaya, Yu Yamaguchi, Ami Watanabe, Hiroaki Yamamoto, Shota Mochizuki, Ryosuke Saio, Takashi Noguchi, Takeshi Oishi, Takaaki Sato, Noritaka Chida
Summary: The total synthesis of paclitaxel is achieved through a double Rubottom oxidation of the bis(silyl enol ether) derived from a tricarbocyclic diketone, efficiently installing a bridgehead olefin and C-5/C-13 hydroxy groups in one step. Additionally, a novel Ag-promoted oxetane formation method is used to smoothly construct the tetracyclic framework of paclitaxel.
Article
Chemistry, Organic
Masaki Ohta, Shota Kato, Tomoya Sugai, Haruhiko Fuwa
Summary: The study investigates the synthesis of a series of 2,5-substituted tetrahydrofuran derivatives through cobalt-catalyzed Hartung-Mukaiyama cyclization. The stereochemical outcome of the reaction is dependent on the substitution pattern and relative configuration of gamma-hydroxy olefins. Appropriately substituted gamma-hydroxy olefins can result in diastereoselective formation of 2,5-trans-substituted tetrahydrofuran derivatives.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Food Science & Technology
Sandra Raposo-Garcia, M. Carmen Louzao, Haruhiko Fuwa, Makoto Sasaki, Carmen Vale, Luis M. Botana
Summary: Ciguatoxins are causative compounds of ciguatera fish poisoning and their potency is determined as CTX1B > CTX3B > CTX4A > gambierol > gambiemne > MTX3. The activation voltage of sodium channels is more sensitive in detecting ciguatoxins than their effect on peak sodium current amplitude.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Daichi Mizukami, Kei Iio, Mami Oda, Yu Onodera, Haruhiko Fuwa
Summary: Tetrahydropyran-containing macrolactones were synthesized using gold and ruthenium catalysis through a three-step reaction sequence, demonstrating high synthetic efficiency and good diastereoselectivity. The synthesis of an anticancer marine macrolide showcased the potential application of this reaction sequence in the synthesis of natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Kazuki Nakazato, Mami Oda, Haruhiko Fuwa
Summary: An 11-step synthesis of (+)-neopeltolide was developed using a tandem macrocyclization/transannular pyran cyclization strategy for stereo-controlled construction of the neopeltolide macrolactone. The C1-C7 carboxylic acid and the C8-C16 alcohol were prepared in six steps from (R)- and (S)-epichlorohydrin, respectively. The side chain was synthesized in six steps from ethyl 4-oxazolecarboxylate through palladium-catalyzed cross-couplings. The synthesis was completed by a Mitsunobu reaction of the neopeltolide macrolactone and the side chain.
Article
Food Science & Technology
Evelyne Benoit, Sebastien Schlumberger, Jordi Molgo, Makoto Sasaki, Haruhiko Fuwa, Roland Bournaud
Summary: Gambierol inhibits K+ channels in rat fetal adrenomedullary cells, but has no effect on other channels. It does not alter membrane potential or increase catecholamine release events.
Article
Chemistry, Organic
Atsushi Yoshimura, Ryohei Hanzawa, Haruhiko Fuwa
Summary: An Au-catalyzed tandem reaction was developed for the efficient synthesis of pyrrolidine derivatives with a tetrasubstituted carbon stereocenter. The reaction was successfully applied to the asymmetric synthesis of (-)-lepadiformine A, a marine cytotoxic tricyclic alkaloid.
Article
Chemistry, Multidisciplinary
Kazuk i Nakazato, Mami Oda, Haruhiko Fuwa
Summary: The total synthesis of (+)-neopeltolide, a potent antiproliferative marine macrolide natural product, was achieved in 11 steps from a commercially available inexpensive material. The 14-membered macrolactone skeleton with a 2,6-cis-substituted tetrahydropyran ring was synthesized using a macrocyclization/trans-annular pyran cyclization strategy. The synthesis of the oxazole-containing side chain was achieved through palladium-catalyzed cross-coupling reactions. Additionally, the total synthesis of (+)-9-epi-neopeltolide was accomplished in 12 steps by stereochemical diversification at the C9 position.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2023)
Article
Chemistry, Multidisciplinary
Keisuke Murata, Hirotoshi Mori, Haruhiko Fuwa
Summary: In this study, the application of GIAO NMR chemical shift calculation and DP4-type statistical analyses in the stereochemical assignment of marine macrolide natural products was assessed. The incorrect relative configurations in the originally proposed structures were identified and the effect of cumulative Boltzmann population level on DP4+ probability was examined. Additionally, the GIAO NMR chemical shift calculation/DP4-type statistical analysis was successfully applied to the determination of the relative configuration of leptolyngbyalide A-C/oscillariolide macrolactone.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2022)
Article
Chemistry, Organic
Ryohei Hanzawa, Haruhiko Fuwa
Summary: A collective asymmetric total synthesis of marine tricyclic alkaloids, cylindricines A-H, as well as the proposed structures of cylindricines I and J, was accomplished from a single common spirocyclic pyrrolidine intermediate in a concise manner. A tandem chemoselective oxidation/intramolecular aza-Michael addition/epimerization strategy was utilized to successfully construct the tricyclic skeleton. This work presents a versatile synthetic approach to the cylindricine family of marine tricyclic alkaloids.
Article
Chemistry, Organic
Yoshihiro Goda, Haruhiko Fuwa
Summary: The total synthesis of (-)-enigmazole B was achieved for the first time using a series of efficient chemical reactions, including olefin cross-metathesis, hemiacetalization/intramolecular oxa-Michael addition sequence, Sonogashira cross-coupling, chemo- and regioselective Au-catalyzed intramolecular alkyne hydroalkoxylation, and Yamaguchi macrolactonization.
Article
Chemistry, Organic
Riko Minami, Tsubasa Kasai, Keisuke Murata, Haruhiko Fuwa
Summary: In this study, a convergent total synthesis of (+)-muricatetrocin B, a tetrahydrofuran-containing acetogenin with potent and selective cytotoxicity against HT-29 human colon adenocarcinoma cell line, was achieved in 13 steps. The synthesis is highlighted by a late-stage sequential olefin cross-metathesis/Hartung-Mukaiyama cyclization for the assembly of the 2,5-trans-substituted tetrahydrofuran ring.
Article
Chemistry, Organic
Haruhiko Fuwa
Summary: In this paper, the development of a new strategy for streamlined synthesis of tetrahydropyran-embedded macrolactones is summarized, as well as its successful implementation in the total synthesis of two natural products. The method enables a reduction in steps and an improvement in synthesis efficiency.
Article
Chemistry, Multidisciplinary
Hayato Nakagawa, Haruhiko Fuwa
Summary: Stereodivergent synthesis of 2,5-disubstituted pyrrolidines was achieved through a Au-catalyzed tandem intramolecular alkyne hydroamination/iminium formation/Et3SiH reduction. The stereochemical outcome could be switched by selecting an appropriate nitrogen protecting group. Total synthesis of a diastereomeric pair of alkaloid natural products, monomorine I and indolizidine 195B, was successfully accomplished to demonstrate the synthetic utility of the tandem reaction.
CHEMICAL COMMUNICATIONS
(2023)
Review
Chemistry, Organic
Haruhiko Fuwa
Summary: This review summarizes recent examples of structure determination, correction, and disproof of structurally complex marine polyketide macrolides through chemical synthesis, highlighting the scope and limitation of current NMR-based structure analysis and the crucial role of chemical synthesis in structure elucidation.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Shota Kato, Daichi Mizukami, Tomoya Sugai, Masashi Tsuda, Haruhiko Fuwa
Summary: This study reports the first total synthesis of amphirionin-2, determination of its absolute configuration, and reassignment of certain relative configurations. The synthesis involved cobalt-catalyzed cyclization of gamma-hydroxy olefins and a late-stage Stille-type coupling, leading to the successful production and comparison of four candidate diastereomers.
