RESUMEN
Oxidative degradation and rearrangement of polycyclic polyprenylated acylphloroglucinols (PPAPs) has created diverse families of unique natural products that are attractive targets for biomimetic synthesis. Herein, we report a racemic synthesis of hyperibrin A and its oxidative radical cyclization to give yezo'otogirin C, followed by epoxidation and House-Meinwald rearrangement to give hypermogin D. We also investigated the biomimetic synthesis of norascyronone A via a similar radical cyclization pathway, with unexpected results that give insight into its biosynthesis.
Asunto(s)
Productos Biológicos , Materiales Biomiméticos , Floroglucinol , Terpenos , Productos Biológicos/síntesis química , Productos Biológicos/química , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Estructura Molecular , Floroglucinol/síntesis química , Floroglucinol/química , Terpenos/síntesis química , Terpenos/químicaRESUMEN
A biomimetic approach to total synthesis can offer several benefits, including the development of cascade reactions for the rapid generation of molecular complexity, and guidance in the structure revision of old natural products and the anticipation of new ones. Herein, we describe how a biomimetic synthesis of bruceol, a pentacyclic meroterpenoid, led to the anticipation, isolation, and synthesis of isobruceol. The key step in the synthesis of both bruceol and isobruceol was an intramolecular hetero-Diels-Alder reaction of an o-quinone methide that was formed by dearomatization of an electron-rich chromene. The synthesis of an elusive biosynthetic intermediate also allowed a concise synthesis of eriobrucinol via a photochemical [2 + 2] cycloaddition. Furthermore, some speculation on the biosynthesis of prenylated bruceol derivatives inspired the development of a Claisen/Cope/Diels-Alder cascade reaction. We also report the generation of halogenated bruceol derivatives and the synthesis of several protobruceol natural products using singlet oxygen ene reactions.
Asunto(s)
Productos Biológicos , Biomimética , Benzopiranos , Reacción de Cicloadición , TerpenosRESUMEN
Reinvestigation of the coumarin meroterpenoids of Philotheca myoporoides using pressurized hot water extraction (PHWE) procedures led to the isolation of prenylbruceol A, a proposed biosynthetic precursor of seven previously reported bruceol derivatives, prenylbruceols B-H. Protobruceol-I, ostruthin, dipetalactone, and a new dihydrocoumarin natural product were isolated alongside prenylbruceol A. A biomimetic singlet oxygen ene reaction of prenylbruceol A allowed the semisynthesis of prenylbruceols B, C, and D.
Asunto(s)
Productos Biológicos/aislamiento & purificación , Biomimética , Rutaceae/química , Estructura Molecular , Oxidación-Reducción , Análisis Espectral/métodosRESUMEN
The total synthesis of nyingchinoidsâ A and B has been achieved through successive rearrangements of a 1,2-dioxane intermediate that was assembled using a visible-light photoredox-catalysed aerobic [2+2+2] cycloaddition. Nyingchinoidâ D was synthesised with a competing [2+2] cycloaddition. Based on NMR data and biosynthetic speculation, we proposed a structure revision of the related natural product rasumatraninâ D, which was confirmed through total synthesis. Under photoredox conditions, we observed the conversion of a cyclobutane into a 1,2-dioxane through retro-[2+2] cycloaddition followed by aerobic [2+2+2] cycloaddition.
Asunto(s)
Materiales Biomiméticos/síntesis química , Luz , Terpenos/síntesis química , Materiales Biomiméticos/química , Catálisis , Estructura Molecular , Oxidación-Reducción , Procesos Fotoquímicos , Estereoisomerismo , Terpenos/químicaRESUMEN
The first total synthesis of bruceol has been achieved using a biomimetic cascade cyclization initiated by a stereoselective Jacobsen-Katsuki epoxidation (and kinetic resolution) of racemic protobruceol-I. A bacterial cytochrome P450 monooxygenase was also found to catalyze the conversion of protobruceol-I into bruceol. The first full analysis of the NMR data of natural bruceol suggested that "isobruceol" was a previously unrecognized natural product also isolated from Philotheca brucei. This was confirmed by the re-isolation, synthesis, and X-ray analysis of isobruceol. In total, eight stereoisomers and structural isomers of bruceol have been synthesized in a highly divergent approach.
Asunto(s)
Productos Biológicos/metabolismo , Materiales Biomiméticos/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Compuestos Heterocíclicos de 4 o más Anillos/metabolismo , Terpenos/metabolismo , Biocatálisis , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Materiales Biomiméticos/química , Materiales Biomiméticos/aislamiento & purificación , Cristalografía por Rayos X , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Modelos Moleculares , Estructura Molecular , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
A simple method for the C-4 alkylation of isoquinolines is described using benzoic acid as a nucleophilic reagent and vinyl ketones as an electrophile. The reaction shows tolerance for substitution at C-3, and C-5-C-8 positions as well as allowing some variation of the vinyl ketone electrophiles. The products contain a carbonyl that can act as a synthetic handle for further manipulations giving esters, amines, or simple alkyl products.
RESUMEN
The total synthesis of (-)-γ-lycorane (10 steps) and synthesis of (±)-γ-lycorane (8 steps) was completed from cyclohexenone. A new two step hydrogen borrowing alkylation of an aziridinyl alcohol, coupled with a Ph* (Me5C6) deprotection/cyclisation procedure was developed for de novo formation of the fused 6,5 heterocyclic ring. This work is one of the first examples of hydrogen borrowing C-C bond formation being used as a key step in a total synthesis project.
Asunto(s)
Alcaloides de Amaryllidaceae , Hidrógeno , Alquilación , Alcaloides de Amaryllidaceae/química , Ciclización , Hidrógeno/químicaRESUMEN
Total synthesis of the Rhododendron meroterpenoids rubiginosins A and G, which both contain unusual 6-6-6-4 ring systems, has been achieved using a bioinspired cascade approach. Stepwise synthesis of these natural products, and the related 6-6-5-4 meroterpenoids fastinoid B and rhodonoid B, from naturally occurring chromene precursors is also reported.
Asunto(s)
Benzopiranos/química , Productos Biológicos/química , Rhododendron/química , Terpenos/síntesis química , Biomimética , Estructura Molecular , Terpenos/químicaRESUMEN
A divergent, three-step total synthesis of rhodonoids C and D has been achieved using a biosynthetically inspired, acid-catalyzed cascade cyclization of an epoxy-chromene that involves the presumed intermediacy of o-quinone methides. Application of a similar strategy also allowed synthesis of the alkaloid murrayakonine D.