RESUMO
Described herein is a synthetic strategy for the total synthesis of (±)-phomoidrideâ D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.
Assuntos
Anidridos Maleicos/síntese química , Compostos Bicíclicos com Pontes/química , Ciclização , Reação de Cicloadição , Oxirredução , EstereoisomerismoRESUMO
Three stereoselective syntheses and the physicochemical properties of trans,trans-5-(4-ethoxy-2,3-difluorophenyl)-2-(4-propylcyclohexyl)tetrahydropyran, which is an important liquid-crystal compound with a large negative dielectric anisotropy (Δε=-7.3), are described. The key step in the construction of the trans-2,5-disubstituted tetrahydropyran ring in the first approach involved a benzylic cation mediated intramolecular olefin cyclization of a 2-allyloxy-1-arylethanol derivative. The second method included the Et2 Zn-induced 1,2-aryl shift of a bromohydrin obtained from a hetero-Diels-Alder reaction, followed by stereoselective bromination. The third approach utilized the hetero-Diels-Alder reaction of trans-4-propylcyclohexanecarboxaldehyde and a 2-aryl-3-(trimethylsilyl)oxy-1,3-butadiene, followed by stereoselective protonation. From results obtained by using a quantum chemical calculation method, the reason why the target compound shows a large negative Δε value is discussed.
RESUMO
An efficient and highly stereoselective approach toward the phomoidride family of natural products is described. The carbocyclic core structure was assembled using a tandem phenolic oxidation/Diels-Alder cycloaddition and a tandem 5-exo-trig/5-exo-trig radical cyclization to deliver an isotwistane intermediate that, upon a late-stage xanthate-initiated Grob fragmentation, furnishes the requisite bicyclo[4.3.1]decene.
Assuntos
Alcenos/química , Produtos Biológicos/química , Produtos Biológicos/síntese química , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/síntese química , Anidridos Maleicos/química , Anidridos Maleicos/síntese química , Ciclização , Estrutura Molecular , Oxirredução , EstereoisomerismoRESUMO
Described is the construction of the N-methylwelwitindolinone C core via an efficient strategy that employs a sequential rhodium carbenoid-mediated O-H insertion, Claisen rearrangement and transannular [3+2] nitrone cycloaddition.
RESUMO
Inspired by the success of fluorinated corticosteroids in the 1950s and fluoroquinolones in the 1980s, fluorine-containing pharmaceuticals, which are also known as fluoro-pharmaceuticals, have been attracting attention for more than half of a century. Presently, about 20% of the commercial pharmaceuticals are fluoro-pharmaceuticals. In this mini-review, we analyze the prevalence of fluoro-pharmaceuticals in the market and categorize them into several groups based on the chemotype of the fluoro-functional groups, their therapeutic purpose, and the presence of heterocycles and/or chirality to highlight the structural motifs, patterns, and promising trends in fluorine-based drug design. Our database contains 340 fluoro-pharmaceuticals, from the first fluoro-pharmaceutical, Florinef, to the latest fluoro-pharmaceuticals registered in 2019 and drugs that have been withdrawn. The names and chemical structures of all the 340 fluorinated drugs discussed are provided in the Supporting Information.
RESUMO
A convergent route to (-)-candelalide A involved the union of a trans-decalin portion (AB ring) and a gamma-pyrone moiety through the C16-C3' bond to assemble the whole carbon framework and subsequent formation of the dihydropyran ring (C ring) as the crucial steps. A strategic [2,3]-Wittig rearrangement was employed for establishing the stereogenic center at C9 and an exo-methylene function at C8 present in the decalin portion. [reaction: see text]
Assuntos
Diterpenos/química , Diterpenos/síntese química , Imunossupressores/química , Imunossupressores/síntese química , Canal de Potássio Kv1.3/antagonistas & inibidores , Pironas/química , Pironas/síntese química , Ascomicetos/química , Estrutura Molecular , EstereoisomerismoRESUMO
[reaction: see text] The first enantioselective total synthesis of otteliones A and B, biologically important and structurally novel natural products, has been successfully achieved. This total synthesis fully confirms the absolute configuration of these natural products.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Cicloexanonas/síntese química , Hydrocharitaceae/química , Modelos Químicos , Estrutura Molecular , EstereoisomerismoRESUMO
[reaction: see text] A new strategy directed toward the total synthesis of stachyflin, a potent and novel anti-influenza A virus agent isolated from a microorganism, has been presented through the enantioselective synthesis of the tetracyclic core structure. The synthetic method features a BF(3) x Et(2)O-induced domino epoxide-opening/rearrangement/cyclization reaction as the key step.
Assuntos
Antivirais/síntese química , Vírus da Influenza A , Sesquiterpenos/síntese química , Antivirais/química , Ciclização , Estrutura Molecular , Sesquiterpenos/química , Stachybotrys/químicaRESUMO
Enantioselective total synthesis of (+)-ottelione A (1) and (-)-ottelione B (2), novel and potent antitumor agents from a freshwater plant, and (+)-3-epi-ottelione A (3), the earlier proposed stereostructure of 1, was efficiently achieved starting from the known tricyclic compound 10. The synthesis involved the following key steps: i) coupling reactions of aldehydes 8 and 9 with the aromatic portion 7 (8+7-->15 and 9+7-->27), ii) base-induced hemiacetal-opening/epimerization reactions of the cyclic hemiacetals 6 and 27 (6-->17 and 27 a-->26 a), and iii) Corey-Winter's reductive olefination of the cyclic thiocarbonates 21 and 36 (21-->22 and 36-->37). The present total synthesis fully established the absolute configuration of these natural products. The cell growth inhibition profile, COMPARE analysis, and tubulin inhibitory assay of (+)-3-epi-ottelione A (3) and its O-acetyl derivative 24 demonstrated that these unnatural substances could be prominent lead compounds for the development of anticancer agents with a novel mode of action.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Cicloexanonas/síntese química , Cicloexanonas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cicloexanonas/química , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Estereoisomerismo , Tubulina (Proteína)/metabolismoRESUMO
An enantioselective synthesis of the fully elaborated tricyclic decahydrofluorene core (ABC-ring system) of GKK1032s, novel antimicrobial and antitumor agents, has been accomplished for the first time by employing a highly diastereoselective intramolecular Diels-Alder (IMDA) reaction. The key substrate for the IMDA reaction was efficiently prepared through (i) an intermolecular Diels-Alder reaction between a siloxydiene and an optically active enone derived from D-mannitol to construct the appropriately functionalized C-ring and (ii) CuCl-promoted Stille coupling of an (E)-vinyl iodide and a vinylstannane to install the requisite triene side chain as the crucial steps.