The First Total Synthesis of Dragmacidin D

Abstract

Material and Methods. Unless stated otherwise, reactions were performed in flame-dried glassware under a nitrogen or argon atmosphere using dry, deoxygenated solvents. All other commercially obtained reagents were used as received. Solvents were dried by passage through an activated alumina column under argon. Reaction temperatures were controlled by an IKAmag temperature modulator. Thin-layer chromatography (TLC) was performed using E. Merck silica gel 60 F254 precoated plates (0.25 mm) and visualized by UV or anisaldehyde staining. ICN Silica gel (particle size 0.032-0.063 mm) was used for flash chromatography. Disposable SepPak C 18 Vac Cartridges were purchased from Waters and used for all reversed-phase filtrations.HPLC analysis was performed on a Beckman Gold system using a Rainin C 18 , Microsorb MV, 5mm, 300 x 4.6 mm reversed-phased column in 0.1% (wt/v) TFA with acetonitrile as eluent and a flow rate of 1.0 mL/min, gradient elution of 1.25% acetonitrile/min. Preparatory reversed-phase HPLC was performed on a Beckman HPLC with a Waters DeltaPak 25 x 100 mm, 100 mm C 18 column equipped with a guard, 0.1% (wt/v) TFA with acetonitrile as eluent, and gradient elution of 0.50% acetonitrile/min. For all reversed-phase purifications, water (18MW) was obtained from a Millipore MiliQ water purification system and TFA from Halocarbon, Inc.

Palladiumkatalysierte Kreuzkupplungen in der Totalsynthese

“…[149] Palladiumvermittelte Reaktionen waren auch hilfreich bei der Synthese des Pyrrol-Kupplungspartners 166, bei der als entscheidender Schritt zur Kohlenstoff-Kohlenstoff-Kupplung eine oxidative Heck-Cyclisierung des monosubstituierten Pyrrols 162 die sterisch befrachtete bicyclische Struktur 165 mit anelliertem Pyrrolring in guter Ausbeute und als einziges Regio-und Stereoisomer ergab. Diese Reaktion, die einem verwandten Beispiel in der Synthese von Okaramin N (55; siehe Schema 11, Abschnitt 2) ähnelt, gelang zwar nicht mit katalytischen Palladiummengen, ist aber dennoch bemerkenswert, da dabei die C-H-Bindung an der desaktivierten C3-Position der Acylpyrrol-Einheit funktionalisiert wird.…”

A unified synthetic approach to the pyrazinone dragmacidins

“…This effort stands as the only completed total synthesis of dragmacidin D to date. [23][24][25] The total synthesis of dragmacidin F Having developed a strategy to construct the bis(indole)pyrazinone core of dragmacidin D (5), we set out to apply our Pd(0) halogen-selective Suzuki coupling methodology to the synthesis of related natural products. We hypothesized that our approach could be amenable to the preparation of the antiviral agent dragmacidin F, 3f,g which is perhaps the most challenging target of the dragmacidin natural products.…”

One-Pot N-Arylation of Indoles Directly from N-Arylsulfonylindoles via Consecutive Deprotection and SNAr Reactions with Activated Aryl Halides

“…[18][19][20][21] The arylsulfonyl groups are useful for protecting groups for the NH group of the indoles because of their robust behavior under a wide variety of reaction conditions. [22][23][24][25] Recently, many methods for the deprotection of N-tosylated indoles have been described, such as highly basic NaOH or KOH in alcohol, 26) tetra-n-butylammonium fluoride (TBAF) in refluxing tetrahydrofuran (THF), 27) and Mg in MeOH. 28) However, to the best of our knowledge, N-arylsulfonylindoles have never been used as latent indoles in the SNAr reactions with aryl halides to prepare N-arylindoles directly.…”