RESUMO
Conversion of a simple furan into the ABCD-ring skeleton of the azaspiracids via a singlet oxygen-initiated one-pot process has been accomplished.
Assuntos
Furanos/química , Furanos/síntese química , Toxinas Marinhas/química , Toxinas Marinhas/síntese química , Compostos de Espiro/química , Compostos de Espiro/síntese química , Estrutura Molecular , Oxigênio SingleteRESUMO
Photooxygenations of 2-(γ,ε-dihydroxyalkyl) furans in H(2)O followed by in situ reduction and ketalization affords, in one synthetic operation, DE-bicyclic ketals of the pectenotoxins.
RESUMO
In this article, we explore how changes in the positioning of pendant hydroxyl functionalities in the photooxygenation substrate dramatically alter the course of furan oxidations that are initiated by singlet oxygen; and, how these different reactivities can be harnessed through cascade reaction sequences to access, rapidly and effectively, a broad range of important natural product motifs.
Assuntos
Produtos Biológicos/química , Furanos/química , Oxigênio/química , Oxirredução , Processos Fotoquímicos , Oxigênio Singlete/químicaRESUMO
The key ABC-ring motif of the pectenotoxins has been synthesized, starting from a simple and readily accessible difuran precursor, using a complex singlet oxygen-mediated cascade reaction sequence.
Assuntos
Furanos/química , Lactonas/síntese química , Macrolídeos/síntese química , Piranos/síntese química , Oxigênio Singlete/química , Furanos/síntese química , Lactonas/química , Macrolídeos/química , Estrutura Molecular , Piranos/química , EstereoisomerismoRESUMO
Photooxygenation of 2-(gamma-hydroxyalkyl)furans followed by dehydration affords, in one synthetic operation and in high yield, gamma-spiroketal gamma-lactones. This newly developed technology was successfully applied to the synthesis of three different epimers of pyrenolide D, as well as to the first synthesis of the anticancer natural product crassalactone D and its C4-epimer.
Assuntos
Furanos/química , Lactonas/química , Compostos de Espiro/química , Compostos de Espiro/síntese química , Furanos/síntese química , Peróxido de Hidrogênio/química , Hidróxidos/químicaRESUMO
Photooxygenation of 2-(beta-hydroxyalkyl) furans affords, in one synthetic operation and in high yields, 3-keto-tetrhydrofuran motifs via intramolecular Michael-type addition to the 1,4-enedione intermediate.
Assuntos
Furanos/síntese química , Oxigênio Singlete/química , Furanos/química , Reprodutibilidade dos TestesRESUMO
[Reaction: see text]. Singlet oxygen is a powerful tool in the armament of the synthetic organic chemist and possibly in that of nature itself. In this Account, we illustrate a small selection of the many ways singlet oxygen can be harnessed in the laboratory to aid in the construction of the complex molecular motifs found in natural products. A more philosophical question is also addressed: namely, how much do singlet oxygen oxidations influence the biogenesis of these natural products? All the synthetic examples surveyed in this Account can be characterized as belonging to the same class because they all involve the oxidation of a substituted furan nucleus by singlet oxygen. Readily accessible and relatively simple furans can be transformed into a host of complex motifs present in a diverse range of natural products by the action of singlet-oxygen-mediated reaction sequences. These reactions are highly advantageous because they frequently deliver a rapid and dramatic increase in molecular complexity in high yield. Furthermore, an unusually wide structural diversity is exhibited by the molecular motifs obtained from these reaction sequences. For example, relatively minor modifications to the starting substrate and to the reaction conditions may lead to products as variable as spiroketal lactones, 3-keto-tetrahydrofurans, various types of bis-spiroketals, 4-hydroxy cyclopentenones, or spiroperoxylactones. In addition, two more specialized examples are discussed in this Account. The core of the prunolide molecules and the chinensine family of natural products were rapidly synthesized using effective and short singlet oxygen mediated strategies; this adds weight to the assertion that singlet oxygen is a very effective moderator of complex cascade reaction sequences. We also show how our synthetic investigations have provided evidence that these same strategies might be used in the biogenesis of these molecules. In the cases of the chinensines and the litseaverticillols, an entire and diverse family of natural products was synthesized beginning from known naturally occurring furan-bearing terpenes. Additionally, in several cases, intermediates in our syntheses have been isolated from natural sources, which suggests that we have followed the same synthetic paths as nature. Certainly, the limit of the synthetic potential of singlet oxygen has not yet been reached, and we can look forward to seeing the boundaries expand in the future in a slew of new and interesting ways.
Assuntos
Produtos Biológicos/síntese química , Furanos/química , Oxigênio/química , Oxigênio Singlete/química , Produtos Biológicos/químicaRESUMO
Singlet oxygen (1O2) proves to be a powerful tool in mediating the one-pot synthesis of a salinomycin-type [6,6,5]-bis-spiroketal unit starting from a suitably substituted furan nucleus.
Assuntos
Furanos/química , Oxigênio/química , Compostos de Espiro/síntese química , Estrutura Molecular , Compostos de Espiro/químicaRESUMO
[reaction: see text] A versatile and general method for the biomimetic construction of [5,5,5]- and [6,5,6]-bis-spiroketals, starting from easily accessible furan nuclei, by means of a powerful one-pot singlet oxygen-mediated cascade sequence is reported.
RESUMO
[structure: see text]. An unusual regioselectivity pattern for the ortho lithiation of 3-aryl and 3-styryl furans has been uncovered wherein lithiation occurs preferentially at the sterically encumbered 2-position. The results are attributed, at least in part, to stabilization of the intermediate furyl anion by through-space donation of pi-electron density from the substituent appended at the 3-position to the lithium cation. This ortho lithiation reaction may be applied as a useful synthetic tool for accessing 2,3-disubstituted furans.
RESUMO
[reaction: see text] A highly efficient and rapid four-step synthesis of the bis-spiroketal core of the prunolide natural products, starting from furan itself, is described. The key step and culmination of the synthesis, responsible for zipping up the spirocyclic core, is a singlet oxygen-orchestrated cascade sequence in which a double photooxygenation of a 1,2-difuryl alkene precursor precedes dehydration and spirocyclization to furnish the intact prunolide core.
Assuntos
Furanos/síntese química , Toxinas Marinhas/síntese química , Oxigênio Singlete/química , Compostos de Espiro/síntese química , Ciclização , Estrutura MolecularRESUMO
[reaction: see text] Stereospecific RCM reaction of 7 (R1 = Me) results in the formation of (Z)-11-membered macrocycle 9c. Cascade RCM/ROM/RCM transformation of 7 (R1 = H) affords the thermodynamically more stable spirocycle product 12.