Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates

A palladium-catalyzed enantioselective redox-relay Heck reaction of 2-indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine-oxazoline ligand. Tuning the electronics of the indole, through judicious choice of N-protecting group, is required to ensure selective β-hydride elimination away from the indole core. Utility of this method is highlighted in a modular formal synthesis of an S1P₁ agonist precursor developed by Merck.     

An efficient,mild and selective Ullmann‐type N‐arylation of indoles catalysed by Pd immobilized on amidoxime‐functionalized mesoporous SBA‐15 as heterogeneous and recyclable nanocatalyst

A wide range of N‐arylated indoles were selectively synthesized through intermolecular C(aryl)? N bond formation from the corresponding aryl iodides and indoles through Ullmann‐type coupling reactions in the presence of a catalytic amount of Pd immobilized on amidoxime‐functionalized mesoporous SBA‐15 (SBA‐15/AO/Pd(0)) under mild reaction conditions. These cross‐coupled products were obtained in excellent yields under mild conditions at extremely low palladium loading (ca 0.3 mol%), and the heterogeneous catalyst can be readily recovered by simple filtration and reused seven times with loss in its activity. Copyright © 2015 John Wiley & Sons, Ltd.     

17β-雄甾醇-[3,2-b]-吲哚的合成

以表雄酮为原料,经羟基氧化、羰基保护、还原、Fischer吲哚环化等反应合成了17-β-醇-雄甾-[3,2-b]-吲哚(5),总收率43.2%,其结构经1H NMR,IR和MS确证。生物活性初步测试结果表明:与雄诺龙相比,5对淡色库蚊的杀虫活性显著提高,在浓度为400 mg·L-1时,杀虫率为41.5%。     

Alcohols as Fluoroalkyl Synthons: Ni-catalyzed Dehydrogenative Approach to Access Polyfluoroalkyl Bis-indoles

An acceptorless dehydrogenative strategy for the synthesis of polyfluoroalkylated bis-indoles is described by employing an earth-abundant nickel-based catalytic system under air. The notable feature of the present transformation is the use of bench stable and easily affordable polyfluorinated alcohols without any pre-functionalization for the introduction of precious polyfluoroalkyl groups. The developed straightforward protocol accomplished biologically relevant fluoroalkyl bis-indoles in a sustainable fashion. Extensive DFT study predicts the unique role of indole molecules which stabilizes the transition states during the dehydrogenation process of polyfluorinated alcohols, presumably through non-covalent π⋅⋅⋅π and H-bonding interactions.     

Mass spectrometry detection of minor new meridianins from the antarctic colonial ascidians Aplidium falklandicum and Aplidium meridianum

Taking into account the broad biological activities found in the meridianin indole alkaloids isolated to date, we have re‐examined the organic extracts of an Antarctic collection of the tunicates Aplidium meridianum and A. falklandicum (Chordata: Ascidiacea) by HPLC in conjunction with a high‐resolution mass spectrometer (HPLC‐MS). A new set of analogs of meridianins A–G has been detected, and their structures are proposed on the basis of the molecular formulae identified by LC‐HRMS analysis using a C18 column with a gradient of water/acetonitrile and an LTQ‐FT‐MS Orbitrap detector. Remarkably, dimers derived from meridianin A and from meridianin B or E were also detected. Our findings provide further evidence of the broad variability within the meridianin‐like derivatives of this highly bioactive alkaloid family. Copyright © 2015 John Wiley & Sons, Ltd.     

Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem

Penitrem A is one of the most elaborated members of the fungal indole diterpenes. Two separate penitrem gene clusters were identified using genomic and RNA sequencing data, and 13 out of 17 transformations in the penitrem biosynthesis were elucidated by heterologous reconstitution of the relevant genes. These reactions involve 1) a prenylation‐initiated cationic cyclization to install the bicyclo[3.2.0]heptane skeleton (PtmE), 2) a two‐step P450‐catalyzed oxidative processes forming the unique tricyclic penitrem skeleton (PtmK and PtmU), and 3) five sequential oxidative transformations (PtmKULNJ). Importantly, without conventional gene disruption, reconstitution of the biosynthetic machinery provided sufficient data to determine the pathway. It was thus demonstrated that the Aspergillus oryzae reconstitution system is a powerful method for studying the biosynthesis of complex natural products.     

Computational Study of the Electron Spectra of Vapor-Phase Indole and Four Azaindoles

After geometry optimization, the electron spectra of indole and four azaindoles are calculated by density functional theory. Available experimental photoemission and excitation data for indole and 7-azaindole are used to compare with the theoretical values. The results for the other azaindoles are presented as predictions to help the interpretation of experimental spectra when they become available.     

Crowned Macrocycles Containing Two Pyrrolo[1,2-a] Indoles Created By Intramolecular Fusion

Heterocyclic fused-ring systems are of utmost importance because of their presence in many natural products with biological activity. Pyrroloindoles are tricyclic heterocycles that are present in various bioactive and medicinally valuable compounds. Herein, we report the synthesis of phenylene-bridged bis-pyrrolo[1,2-a]indole crowned macrocycles 1 – 3 in which the pyrrolo[1,2-a]indole moieties were formed via intramolecular fusion. The macrocycles were thoroughly characterized by 1D and 2D NMR, HRMS and X-ray crystallographic studies. The X-ray structure revealed that the two pyrrolo[1,2-a]indole moieties were parallel to each other, and one pyrrolo[1,2-a]indole unit was deviated by an angle of 9.54° while the other pyrrolo[1,2-a]indole unit was deviated by an angle of 12.0° from the mean plane defined by 28 core atoms. The macrocycles 1 – 3 absorb in the visible region and readily undergo oxidations because of their electron rich nature. The macrocycles 1 – 3 upon treatment with trifluoroacetic acid (TFA) generates the corresponding cation radicals 1 – 3 ^.+ which were stable in the open air for a week. The cation radicals 1 – 3 ^.+ absorb strongly in the NIR region and the experimental observations on crowned macrocycles 1 – 3 were corroborated by DFT and TD-DFT studies.     

Enantioselective Total Synthesis of (+)-Nordasycarpidone, (+)-Dasycarpidone,and (+)-Uleine

The structure of uleine type alkaloids is characterized by the presence of a bridged tetracyclic hexahydro-1H-1,5-methanoazocino[4,3-b]indole ring system 1 . Various strategies have been developed to access this polycyclic structural motif. We report herein a one-step conversion of appropriately functionalized 1,3,4-trisubstituted cyclopent-1-ene to 1 by way of an integrated oxidation/reduction/cyclization (iORC) process. This domino sequence, initiated by oxidative cleavage of cyclopentene ring, generated subsequently a cyclohexenone, an indole and a 1,3-bridged piperidine ring through formation of one C−C and two C−N bonds. Compound 1 is subsequently converted to nordasycarpidone, dasycarpidone and uleine. The chirality of the molecule was introduced by enzymatic desymmetrization of commercially available meso cis-3,5-diacetoxy-1-cyclopentene.