Article
Chemistry, Multidisciplinary
Yan Zhang, Yuye Chen, Manrong Song, Bin Tan, Yujia Jiang, Chongyuan Yan, Yuyang Jiang, Xinyue Hu, Chengqian Zhang, Wenqing Chen, Jing Xu
Summary: This article reports on the divergent total syntheses of three calyciphylline A-type alkaloids. The synthesis strategy involves efficient and diverse late-stage divinyl carbinol rearrangements, including an unprecedented oxidative Nazarov electrocyclization, an unusual allylic alcohol rearrangement, and a critical nitrile hydration step using a highly efficient donor-acceptor platinum catalyst. Additionally, the power of selective amide reductions is showcased through novel and classic tactics.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Yi Cui, Jun Ren, Jiayuan Lv, Zhongwen Wang
Summary: An efficient synthesis of the aza-[5.7.6.5] tetracyclic core structure of calyciphylline D-type Daphniphyllum alkaloids has been achieved, featuring diastereoselective cyclopropanation and a [3 + 2] IMCC strategy, as well as gram-scale preparation in each step.
Article
Chemistry, Multidisciplinary
Bingyang Wang, Bo Xu, Wen Xun, Yiming Guo, Jing Zhang, Fayang G. Qiu
Summary: An efficient general strategy for the synthesis of Daphniphyllum alkaloids has been established, leading to the total synthesis of (-)-daphenylline and (-)-himalensine A in 16 and 19 steps, respectively. The synthesis involves various reactions including an enantioselective Mg(ClO4)(2)-catalyzed intramolecular amidocyclization to construct the core structure, a Cu-catalyzed intramolecular cyclopropanation and subsequent phosphine-catalyzed Cope-type rearrangement for the himalensine A scaffold, and a one-pot Diels-Alder/aromatization method for the aromatic skeleton of daphenylline.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Kosuke Okada, Ken-ichi Ojima, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: The synthesis of (+)-pleiocarpamine, (+)-voacalgine A and (+)-bipleiophylline was achieved in this study. The 10-step synthesis of (+)-pleiocarpamine features the construction of stereochemistry at the C16 position by radical cyclization and the synthesis of the highly strained cage-like structure via Pd-catalyzed intramolecular aromatic C-H functionalization. By modifying the biomimetic aerobic oxidative coupling of tryptophane derivatives catalyzed by FePc(CO2H)(8), the oxidative coupling of (+)-pleiocarpamine with pyrocatechuic acid produced (+)-voacalgine A. The total synthesis of (+)-bipleiophylline was completed by the second coupling of (+)-voacalgine A with (+)-pleiocarpamine or the one-pot couplings of 2 equiv of (+)-pleiocarpamine with pyrocatechuic acid.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Jingping Hu, Lian-Dong Guo, Wenqing Chen, Yuyang Jiang, Fan Pu, Chengqing Ning, Jing Xu
Summary: This study reports the first total syntheses of daphnezomine L-type alkaloids, including daphnezomine L methyl ester and calyciphylline K, via late-stage C-N bond activation and a similar strategy for the synthesis of secodaphniphylline-type alkaloid caldaphnidine D. Other key transformations employed in the synthesis include a facile vicinal diol olefination and an efficient radical cyclization cascade. Biological studies indicate that the two synthetic compounds show promising neuroprotective activity.
Article
Chemistry, Organic
Wesley J. Olivier, Alex C. Bissember, Jason A. Smith
Summary: The total syntheses of Stemona alkaloids sessilifoliamides B and D, as well as the second synthesis of sessilifoliamide C, were successfully completed from a simple pyrrole substrate. The bicyclic lactam core was prepared on a gram scale via a Bronsted acid mediated cyclization and controlled oxidation with Dess-Martin periodinane. Yield percentages for the synthesis of sessilifoliamides B, C, and D were 24%, 13%, and 17% respectively, over multiple steps.
Article
Chemistry, Organic
Eunjoon Park, Cheolwoo Bae, Cheon-Gyu Cho, Cheol-Hong Cheon
Summary: The total syntheses of the antirhine alkaloids were achieved through a series of reactions, including the cyanide-catalyzed imino-Stetter reaction and subsequent C-ring formation to generate the key intermediate. The trans-selective installation of the homoallylic alcohol side-chain at C-15 allowed the successful total syntheses of antirhine and its known epimer.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Hongchang Tian, Yinxia Wu, Xiujuan Li, Zhen Hao, Wenyan He, Xiangdi Huang, Wen Chen, Hongbin Zhang
Summary: In this article, we present the first total synthesis of Kopsaporine related alkaloids. Our structure-unit-based strategy utilizes intramolecular Pummerer rearrangement induced nucleophilic cyclization/aza-Prins cyclization to construct the hexahydrocarbazole skeleton, olefin migration vinylogous alkylation to establish the C20 all-carbon quaternary center, iridium complex mediated radical addition to fuse the aspidofractine framework, unprecedented IBX oxidation to introduce the alpha-hydroxyketone moiety, and bioinspired retro-Aldol/Aldol reaction to convert kopsaporine to kopsiloscine A.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Yoshihiro Ataka, Mariko Kitajima, Hayato Ishikawa
Summary: The enantioselective total synthesis of (-)-silicine and (-)-20-episilicine, which contain a chiral piperidine with three contiguous chiral centers (D-ring) and a strained seven-membered ring (C-ring) attached to an indole, has been achieved. The key steps of these syntheses include a chiral secondary amine-catalyzed formal aza-[3 + 3] cycloaddition reaction and Lewis acid-mediated irreversible ring-closing reaction.
Article
Chemistry, Organic
Xinpei Cai, Lei Li, Ye-Cheng Wang, Jianhan Zhou, Mingji Dai
Summary: In this paper, we describe the complete synthesis of phleghenrines A and C from commercially available starting materials in 7 and 8 steps, respectively. Key steps include an inverse electron-demand Diels-Alder reaction between a masked o-benzoquinone and a N-protected enamine to generate a bicyclo[2.2.2]octenone core, a Bu''chner-Curtius-Schlotterbeck one-carbon insertion to expand the bicyclo[2.2.2]octenone to a bicyclo[3.2.2]nonenone, and Trauner's modified 2-pyridone synthesis to install the 2-pyridone moiety.
Article
Chemistry, Multidisciplinary
Feifei He, Shangbiao Feng, Yulong Zhao, Hongliang Shi, Xiaoguang Duan, Huilin Li, Xingang Xie, Xuegong She
Summary: A gold-catalyzed reaction is developed to access tricyclic cores using the commonly shared bicyclic decahydroquinoline motif. These cores are then used for the divergent total syntheses of five Lycopodium alkaloids in a concise manner. Key transformations include ring cyclization, hydration, fragmentation, and construction of specific motifs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Organic
Hongjun Jeon
Summary: The review focuses on the recent 10 total syntheses of cephalotaxine-type alkaloids reported from 2016 to 2021, highlighting synthetic hallmarks and common synthetic routes of this class, revealing the forefront of research in organic chemistry.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Shicheng Jin, Xiangbo Zhao, Dawei Ma
Summary: The study presents a new method for the synthesis of napelline-type alkaloids, achieving the construction of the core structure and characteristic chemical groups through a series of reactions, including conjugate addition and cyclization.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Masahiro Okuyama, Nariyoshi Umekubo, Kenta Akimoto, Takahisa Shimizu, Kazuhiro Kubokoya, Nagayasu Nakajima, Yoshitake Nishiyama, Satoshi Yokoshima
Summary: Total syntheses of fawcettimine-class Lycopodium alkaloids with an imino bridge between C5 and C13 were successfully achieved. Fawcettimine was synthesized for the first time in 10 steps from a known compound, and the characteristic structures, including the imino bridge, were constructed through the formation of a bridgehead imine.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Pei Qu, Scott A. Snyder
Summary: The newly added annotinolides in the Lycopodium family have complex structures, and we have successfully achieved the total synthesis of three members using key operations such as gold(I)-catalyzed Conia-ene reaction and other challenging transformations. Furthermore, efforts to adjust the oxidation states and rearrange ring systems of the natural products shed light on their potential biogenesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Applied
Alexey L. Kaledin, Jose B. Roque, Richmond Sarpong, Djamaladdin G. Musaev
Summary: The study demonstrates a feasible Cu(I)-mediated deconstructive fluorination mechanism for N-benzoylated cyclic amines with Selectfluor (R) through calculations, providing a theoretical basis for the reaction.
TOPICS IN CATALYSIS
(2022)
Review
Chemistry, Multidisciplinary
Vignesh Palani, Melecio A. Perea, Richmond Sarpong
Summary: This review discusses strategies for site-selective functionalization of polyhalogenated arenes and heteroarenes, including traditional reaction types and emerging strategies.
Article
Chemistry, Multidisciplinary
Robert F. Lusi, Goh Sennari, Richmond Sarpong
Summary: A strategy orthogonal to classic approaches and coupled with C-H functionalization methods has been used to achieve the shortest synthesis and divergent syntheses of a sesquiterpenoid longiborneol, providing inspiration for the synthesis of other topologically complex natural products.
Article
Chemistry, Organic
Melissa A. Hardy, Bozhao Nan, Olaf Wiest, Richmond Sarpong
Summary: Computer-assisted synthesis planning is an emerging research area, particularly for complex molecule synthesis. This study presents a case study on pupukeanane natural products, which are complex, marine-derived compounds with unique tricyclic scaffolds. The authors compare proposed synthesis routes generated using the program SynthiaT with previous syntheses of these molecules and propose novel synthesis routes for previously unprepared pupukeanane congeners.
Article
Chemistry, Multidisciplinary
Goh Sennari, Kristen E. Gardner, Stefan Wiesler, Maximilian Haider, Alina Eggert, Richmond Sarpong
Summary: Guided by chemical network analysis, the synthetic studies towards C18- and C19-benzenoid cephalotane-type norditerpenoids were carried out, leading to the construction of core structure in a concise manner and improvement of efficiency through reaction optimization.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Christina G. Na, Suh Hyun Kang, Richmond Sarpong
Summary: A C-C bond cleavage/vinylation/Mizoroki-Heck cascade reaction has been developed to access densely functionalized bicyclo[2.2.2]octane frameworks. The method was successfully applied in the total synthesis of 14- and 15-hydroxypatchoulol, providing unambiguous support for their structures and correcting a misassignment in the isolation report.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Correction
Chemistry, Multidisciplinary
G. Logan Bartholomew, Filippo Carpaneto, Richmond Sarpong
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
G. Logan Bartholomew, Filippo Carpaneto, Richmond Sarpong
Summary: A method for the conversion of pyrimidines into pyrazoles has been achieved guided by computational analysis. The method proceeds under mild conditions, with high yields and tolerance to a wide range of functional groups. It enables the regioselective introduction of N-substitution on the resulting pyrazole.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Brandon A. Wright, Anastassia Matviitsuk, Michael J. Black, Pablo Garcia-Reynaga, Luke E. Hanna, Aaron T. Herrmann, Michael K. Ameriks, Richmond Sarpong, Terry P. Lebold
Summary: Azabicyclo[2.1.1]hexanes (aza-BCHs) and bicyclo[1.1.1]pentanes (BCPs) are attractive sp(3)- rich cores for drug scaffolds. Scaffold hopping between these bioisosteric subclasses through a nitrogen-deleting skeletal edit is described. The strategy involves photochemical cycloadditions and subsequent deamination to afford bridge-functionalized BCPs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Daniel Lucke, Alexander S. Campbell, Martin Petzold, Richmond Sarpong
Summary: Here, a synthesis method of 1-hydroxy-2-naphthoic acid esters through an unexpected Lewis-acid-mediated 1,2-acyl shift of oxabenzonorbornadienes is reported. This method allows the obtaining of novel substitution patterns for 1-hydroxy-2-naphtoic acid esters. A mechanistic proposal and rationale for this transformation, which had been previously incorrectly characterized, is provided.
Review
Chemistry, Multidisciplinary
Ian Bakanas, Robert F. Lusi, Stefan Wiesler, Jack Hayward Cooke, Richmond Sarpong
Summary: The oxidation of unactivated C-H bonds has greatly influenced the synthesis of complex molecules, providing more options for starting materials and simplifying the synthesis planning process. This Review classifies and analyzes different types of C-H oxidation reactions based on their strategic purpose and provides case studies to demonstrate their applications in recent total syntheses.
NATURE REVIEWS CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ian Bakanas, Jess C. Tang, Richmond Sarpong
Summary: This article describes the diversification of tricyclo[3.2.1.0(3,6)]octane scaffolds to synthesize diverse bicyclic scaffolds. The strained tricyclooctanes were prepared in two steps using a blue light-mediated [2+2] cycloaddition. Strategies for the cleavage of this scaffold were then explored, resulting in the selective synthesis of the bicyclo[3.1.1]heptane, bicyclo[3.2.1]octane, and bicyclo[3.2.0]heptane cores. These findings provide a guide for future studies on C-C cleavage reactions in strained carbon frameworks and their application in complex molecule synthesis.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Kunlayanee Punjajom, Paul P. Sinclair, Ishika Saha, Mark Seierstad, Michael K. Ameriks, Pablo Garcia-Reynaga, Terry P. Lebold, Richmond Sarpong
Summary: A modular approach to dihydro-1,2,5-thiodiazole dioxide heterocycles is reported. Mechanistic and computational studies support an unusual 1,2 nitrogen migration mechanism for this transformation.
Article
Chemistry, Multidisciplinary
Lucas T. Gottemann, Stefan Wiesler, Richmond Sarpong
Summary: The methoxime group serves as a versatile directing group for various C-H functionalizations. However, converting methoximes to ketones, which is often desired, typically requires harsh reaction conditions. In this study, we propose a mild and functional group tolerant method for the conversion of methoximes to ketones using photoexcited nitroarenes. The utility of this methodology is demonstrated in the total synthesis of cephanolide D, and mechanistic insight is provided through isotope labeling studies and analysis of reaction byproducts.
Article
Chemistry, Multidisciplinary
Karan Goyal, Garrett A. Kukier, Xiangyang Chen, Aneta Turlik, K. N. Houk, Richmond Sarpong
Summary: A novel synthesis method for aryl-substituted, enantioenriched fulvenes from an oxidative Heck cascade and a rearrangement of a carboxy-substituted spiro[4.4]nonatriene is disclosed. Mechanistic investigations using density functional theory (DFT) calculations and empirical results show that the net transformation occurs through a Pd(ii)-mediated 1,5-vinyl shift from a vinyl-palladium intermediate, which terminates with protodepalladation. This method tolerates a range of electron-rich and deficient arylboronic acids and provides moderate to good yields and enantiomeric ratios of mono- and diaryl substituted annulated fulvenes.
