Ferrocene-Mediated Electrochemical Polycyclization of Malonates.

We report access to the core of biologically relevant aromatic abietane diterpenoids and to the formal synthesis of podocarpic and lambertic acids or γ-lactones via an electrochemical bicyclization process initiated by the ferrocene-mediated anodic oxidation of a malonate via single electron-transfer. This approach permits escaping the use of excess of oxidants such as Mn(OAc) and the associated complicated purification.

Comprehensive Analysis of Local Anesthetics Affecting Adipose Stem Cells In Vitro.

Background: Adipose stem cells (ASCs) hold a great regenerative capacity because of their differentiation capability and their secretory activity. Thus, ASC survival is of great significance during perioperative harvesting. Various local anesthetics are commonly applied during fat grafting procedures.

Collective Total Synthesis of Mavacuran Alkaloids through Intermolecular 1,4-Addition of an Organolithium Reagent.

We report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C-fluorocurine, C-profluorocurine, C-mavacurine, normavacurine, 16-epi-pleiocarpamine and taberdivarine H. We designed a strategy involving late-stage construction of the D ring by Michael addition of a vinylic nucleophile to a 2-indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4-addition of a functionalized vinyl lithium reagent to a readily accessible Michael acceptor with the assistance of the piperidine nitrogen atom through the formation of a complex as suggested by DFT computations.

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition.

A convergent strategy for the synthesis of leustroducsins and phoslactomycins has been designed, relying on the synthesis and the coupling of three main fragments. The central fragment was synthesized via a regio-and stereoselective nitroso Diels-Alder reaction with an enol phosphate, followed by reductive cleavage of the phosphate to the ketone . Coupling studies of this fragment with the lactone fragment was accomplished in a stereoselective fashion through a vinyllithium intermediate.

Total Synthesis of Ophiorrhine A, G and Ophiorrhiside E Featuring a Bioinspired Intramolecular Diels-Alder Cycloaddition.

We report the first total synthesis of the monoterpene indole alkaloids ophiorrhine A via a late stage bioinspired intramolecular Diels-Alder cycloaddition to form the intricate bridged and spirannic polycyclic system. Several strategies were investigated to construct the indolopyridone moiety of ophiorrhiside E, the postulated biosynthetic precursor of ophiorrhine A. Eventually, the Friedel-Crafts-type coupling of N-methyl indolyl-acetamide with a secologanin-derived acid chloride delivered ophiorrhine G.

Pictet-Spengler Reaction for the Chemical Synthesis of Strictosidine.

Strictosidine is the common biosynthetic precursor of Monoterpene Indole Alkaloids (MIA). A practical single-step procedure to assemble strictosidine from secologanin is described via a bioinspired Pictet-Spengler reaction. Mild conditions and purification by crystallization and flash chromatography allow access to the targeted product in fair yield.

Unbiased C3-Electrophilic Indoles: Triflic Acid Mediated C3-Regioselective Hydroarylation of N-H Indoles.

The direct dearomative addition of arenes to the C3 position of unprotected indoles is reported under operationally simple conditions, using triflic acid at room temperature. The present regioselective hydroarylation is a straightforward manner to generate an electrophilic indole at the C3 position from unbiased indoles in sharp contrast to previous strategies. This atom-economical method delivers biologically relevant 3-arylindolines and 3,3-spiroindolines in high yields and regioselectivities from both intra- and intermolecular processes.

Electrochemical Benzylic C-H Functionalization with Isocyanides.

We report the challenging direct carbamoylation or cyanation of benzylic C(sp)-H bonds with an isocyanide via an electrochemical process giving rise to structures that are encountered in several biologically relevant compounds and drugs. This transformation proceeds under mild conditions without the need for any external oxidant and avoids the necessity to start from a prefunctionalized benzylic substrate or the deployment of the cation pool method. The anodic oxidation of the benzylic position and the subsequent addition of the isocyanide lead to the formation of a C-C bond and to a nitrilium cation that hydrolyzes to yield α-aryl acetamide derivatives, whereas the elimination of a -butyl cation delivers α-aryl acetonitrile derivatives.

The Crosstalk Between Adipose-Derived Stem or Stromal Cells (ASC) and Cancer Cells and ASC-Mediated Effects on Cancer Formation and Progression-ASCs: Safety Hazard or Harmless Source of Tropism?

Adipose-derived stem or stromal cells (ASCs) possess promising potential in the fields of tissue engineering and regenerative medicine due to their secretory activity, their multilineage differentiation potential, their easy harvest, and their rich yield compared to other stem cell sources. After the first identification of ASCs in humans in 2001, the knowledge of their cell biology and cell characteristics have advanced, and respective therapeutic options were determined. Nowadays, ASC-based therapies are on the verge of translation into clinical practice.

Synthesis of a Seco -Secologanin Aglycone Analogue of Interest toward Secoiridoids and Monoterpene Indole Alkaloids.

We report the access to an acyclic -secologanin aglycone analogue relevant to secoiridoids and monoterpene indole alkaloids. Its synthesis involved the regioselective allylic alkylation of a linear dienyl carbonate with dimethyl malonate, which was catalyzed by an iridium complex, and an anti-Markovnikov Wacker-type oxidation of the terminal alkene of the branched product that was obtained. The thus-formed aldehyde was engaged in a Pictet-Spengler reaction with tryptamine toward monoterpene indole alkaloids.

The chemistry of mavacurane alkaloids: a rich source of bis-indole alkaloids.

Covering: since early reports up to the end of 2020This review presents a complete coverage of the mavacuranes alkaloids since early reports till date. Mavacuranes alkaloids are a restrictive sub-group of monoterpene indole alkaloids (MIAs), which are represented by their two emblematic congeners, namely, -mavacurine and pleiocarpamine. Their skeleton is defined by a bond between the indolic N1 nitrogen and the C16 carbon of the tetracyclic scaffold of the corynanthe group in MIA.

Bioinspired Early Divergent Oxidative Cyclizations toward Pleiocarpamine, Talbotine, and Strictamine.

Toward the mavacurane and akuammilane monoterpene indole alkaloids, we developed divergent oxidative couplings between the indole nucleus (at N1 or C7) and the C16-malonate of a common tricyclic model related to strictosidine according to a biosynthetic hypothesis postulated by Hesse and Schmid. These oxidative cyclizations led selectively to the formation of the N1-C16 bond of pleiocarpamine or to the C7-C16 bond of strictamine. We were then able to obtain the scaffold of talbotine.

Bioinspired Divergent Oxidative Cyclization from Strictosidine and Vincoside Derivatives: Second-Generation Total Synthesis of (-)-Cymoside and Access to an Original Hexacyclic-Fused Furo[3,2-b]indoline.

The second-generation synthesis of (-)-cymoside as well as the formation of a new hexacyclic-fused furo[3,2-b]indoline framework is reported. After a Pictet-Spengler condensation between secologanin tetraacetate and tryptamine, the course of the cyclization of the 7-hydroxyindolenine intermediate, generated by oxidation with an oxaziridine, depended on the stereochemistry of the 3-position. The 3-(S)-strictosidine stereochemistry delivered efficiently the scaffold of cymoside via intramolecular coupling with the C16-C17 enol ether, while the 3-(R)-vincoside stereochemistry directed towards the reaction with the C18-C19 terminal alkene and the formation of the unexpected caged compound.

Natural Products Originated from the Oxidative Coupling of Tyrosine and Tryptophan: Biosynthesis and Bioinspired Synthesis.

The oxidative coupling of tyrosine and tryptophan units is a pivotal step in the total synthesis of some peptide-derived marine and terrestrial natural products, such as the diazonamides, azonazine and tryptorubin A. This Minireview details the biosynthesis and bioinspired synthesis of natural products with such structures. A special focus is put on the challenges of the synthesis of these natural products and the innovative solutions adopted by synthetic chemists.

Electrochemical synthesis of 3a-bromofuranoindolines and 3a-bromopyrroloindolines mediated by MgBr.

We report an efficient and environmentally friendly electrochemical approach to perform the bromo cyclization of tryptophol, tryptamine and tryptophan derivatives. The 3a-bromofuranoindolines and 3a-bromopyrroloindolines obtained are of interest in the total synthesis of natural products. This dearomative procedure relies on the generation of an electrophilic bromine reagent by the electrochemical oxidation of MgBr2.

Enantioselective Total Synthesis of Cymoside through a Bioinspired Oxidative Cyclization of a Strictosidine Derivative.

The first total synthesis of the caged monoterpene indole alkaloid cymoside is reported. This natural product displays a unique hexacyclic-fused skeleton whose biosynthesis implies an early oxidative cyclization of strictosidine. Our approach to the furo[3,2-b]indoline framework relied on an unprecedented biomimetic sequence which started by the diastereoselective oxidation of the indole ring into a hydroxyindolenine which triggered the addition of an enol ether and was followed by the trapping of an oxocarbenium intermediate.

Dearomatization of 3-Nitroindoles with Highly γ-Functionalized Allenoates in Formal (3+2) Cycloadditions.

3-Nitroindoles are easily reacted with highly substituted γ-allenoates in the presence of a commercially available phosphine catalyst. For instance, allenoates derived from biomolecules such as amino and deoxycholic acids are combined for the first time with 3-nitroindole. The corresponding dearomatized (3+2) tricyclic cycloadducts are obtained as α-regioisomers exclusively.

Synthesis of 3,3-Spirocyclic 2-Phosphonoindolines via a Dearomative Addition of Phosphonyl Radicals to Indoles.

The diastereoselective synthesis of α-amino phosphonate derivatives embedded in spirocyclic indolines is reported. The present method proceeds via the dearomative addition of phosphonyl radicals at the C2-position of the indole nucleus in oxidative conditions followed by the intramolecular trapping of the resulting carbocation before rearomatization. trans-3,3-Spirocyclic 2-phosphonoindolines were thus obtained.

A Fused Hexacyclic Ring System: Diastereoselective Polycyclization of 2,4-Dienals through an Interrupted iso-Nazarov Reaction.

We report an unprecedented domino polycyclization from readily available 2,4-dienals and cyclic α,β-unsaturated imines that is initiated by an iso-Nazarov reaction. This Brønsted acid promoted reaction enables the concomitant formation of four bonds, three cycles, and four contiguous stereogenic centers to yield elaborated structures in a single operation. A range of fused hexacyclic molecules is obtained in a highly diastereoselective manner.

Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for Enantioselective Total Synthesis of Mavacuran Alkaloids.

Reported is the enantioselective total syntheses of mavacuran alkaloids, (+)-taberdivarine H, (+)-16-hydroxymethyl-pleiocarpamine, and (+)-16-epi-pleiocarpamine, and their postulated biosynthetic precursor 16-formyl-pleiocarpamine. This family of monoterpene indole alkaloids is a target of choice since some of its members are subunits of intricate bisindole alkaloids such as bipleiophylline. Inspired by the biosynthetic hypothesis, an oxidative coupling approach from the geissoschizine framework to form the N1-C16 bond was explored.

Electrochemical Dearomative 2,3-Difunctionalization of Indoles.

We report the use of electrochemistry to perform a direct oxidative dearomatization of indoles leading to 2,3-dialkoxy or 2,3-diazido indolines under undivided conditions at a constant current. This operationally simple electro-oxidative procedure avoids the use of an external oxidant and displays excellent functional group compatibility. The formation of the two C-O or C-N bonds is believed to arise from the oxidation of the indoles into radical cation intermediates.

Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for the Total Synthesis of (-)-17-nor-Excelsinidine.

We report the first total synthesis of (-)-17-nor-excelsinidine, a zwitterionic monoterpene indole alkaloid that displays an unusual N4-C16 connection. Inspired by the postulated biosynthesis, we explored an oxidative coupling approach from the geissoschizine framework to forge the key ammonium-acetate connection. Two strategies allowed us to achieve this goal, namely an intramolecular nucleophilic substitution on a 16-chlorolactam with the N4 nitrogen atom or a direct I -mediated N4-C16 oxidative coupling from the enolate of geissoschizine.

Dearomative Diallylation of N-Acylindoles Mediated by FeCl.

Three-dimensional indolines possessing two contiguous-stereogenic centers were obtained stereoselectively via the FeCl-mediated dearomative introduction of two allyl groups to N-acylindoles with allyltrimethylsilane. Synthetic transformations allowed obtention of trans-tetrahydrocarbazoles and an aza[4.4.