On the Valorisation of Chitin-Derived Furans by Milling.

Chitin-derived furans offer a sustainable alternative feedstock for nitrogen appended aromatic compounds. Herein, we address the challenge of using chitin-derived furans, 3-acetamido-5-acetylfuran (3A5AF) and 3-acetamido-5-furfural aldehyde (3A5F), to favour the formation of exo Diels-Alder adducts and 4-acetylaminophthalimides respectively, using a mechanochemical ball-milling technique. Mechanochemical activation is explored through the synthesis of 7-oxa-norbornene backbones with novel substitution pattern from 3A5AF in yields up to 77 % and improved exo:endo selectivity compared to solution-phase reactions.

Acaricidal activity of synthetic spilanthol derivative against ticks of medical and veterinary importance.

The ANESPSAT, a synthetic spilanthol derivative, and its nanoformulation were evaluated against Rhipicephalus microplus and Amblyomma sculptum ticks. ANESPSAT activity was compared with spilanthol and derivatives (ANESPE and others). The compound was synthesized in a gram-scale by a 2-step process, comprising a direct ester amidation and a Horner-Wadsworth- Emmons reaction.

Continuous Flow Generation of Acylketene Intermediates via Nitrogen Extrusion.

A flow chemistry process for the generation and use of acylketene precursors through extrusion of nitrogen gas is reported. Key to the development of a suitable continuous protocol is the balance of reaction concentration against pressure in the flow reactor. The resulting process enables access to intercepted acylketene scaffolds using volatile amine nucleophiles and has been demonstrated on the gram scale.

Continuous flow Meerwein-Ponndorf-Verley reduction of HMF and furfural using basic zirconium carbonate.

Continuous Flow Microreactors and Green Chemistry are areas with promising applications, especially when allied. In this scenario, the main goal of this study was to develop new strategies for the synthesis of bio-based compounds under a flow regime. We worked towards the flow synthesis of furfuryl alcohol and DHMF (dihydroxymethylfuran), from their respective aldehydes, through a Meerwein-Ponndorf-Verley reaction with iso-propanol catalysed by basic zirconium carbonate.

Integrated Batch and Continuous Flow Process for the Synthesis of Goniothalamin.

An integrated batch and continuous flow process has been developed for the gram-scale synthesis of goniothalamin. The synthetic route hinges upon a telescoped continuous flow Grignard addition followed by an acylation reaction capable of delivering a racemic goniothalamin precursor () (20.9 g prepared over 3 h), with a productivity of 7 g·h.

Impact of continuous flow chemistry in the synthesis of natural products and active pharmaceutical ingredients.

We present a comprehensive review of the advent and impact of continuous flow chemistry with regard to the synthesis of natural products and drugs, important pharmaceutical products and definitely responsible for a revolution in modern healthcare. We detail the beginnings of modern drugs and the large scale batch mode of production, both chemical and microbiological. The introduction of modern continuous flow chemistry is then presented, both as a technological tool for enabling organic chemistry, and as a fundamental research endeavor.

Formal Total Synthesis of Actinoranone: Synthesis Approaches and Cytotoxic Studies.

This article describes our efforts toward the total synthesis of actinoranone. Our synthesis strategies rely on a convergent route to connect the terpenoid and polyketide fragments, employing catalysis and powerful classical reactions for the assembly of these key fragments. A new transformation was disclosed during this work, a domino ring-opening and esterification.

Formal Total Synthesis of Actinoranone and Asymmetric Synthesis of Labda-7,13-(E)-dien-15-ol.

The syntheses of the polyketide and terpenoid fragments of actinoranone are reported in a concise fashion, relying on catalytic methods. Minimization on the use of protecting groups and redox reactions allowed the synthesis of the carbon backbone of actinoranone in 20 steps (11 steps for LLS). The asymmetric synthesis of labda-7,13-(E)-dien-15-ol is also disclosed.

Design and synthesis of cenocladamide analogues and their evaluation against breast cancer cell lines.

This work describes the total synthesis of the alkaloid cenocladamide and a concise library of nine structural analogues aiming at their evaluation against the breast cancer cell line MDA-MB-231. The most promising compound (; IC = 6.6 μM) was also evaluated in a panel of seven breast cancer cell lines and two non-tumorigenic cell lines.

A new goniothalamin N-acylated aza-derivative strongly downregulates mediators of signaling transduction associated with pancreatic cancer aggressiveness.

In this study, a novel concise series of molecules based on the structure of goniothalamin (1) was synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (Panc-1). Among them, derivative 8 displayed a low IC50 value (2.7 μM) and its concentration for decreasing colony formation was 20-fold lower than goniothalamin (1).

Design and synthesis of N-acylated aza-goniothalamin derivatives and evaluation of their in vitro and in vivo antitumor activity.

Herein we describe the synthesis of a focused library of compounds based on the structure of goniothalamin (1) and the evaluation of the potential antitumor activity of the compounds. N-Acylation of aza-goniothalamin (2) restored the in vitro antiproliferative activity of this family of compounds. 1-(E)-But-2-enoyl-6-styryl-5,6-dihydropyridin-2(1H)-one (18) displayed enhanced antiproliferative activity.

Flow chemistry syntheses of natural products.

The development and application of continuous flow chemistry methods for synthesis is a rapidly growing area of research. In particular, natural products provide demanding challenges to this developing technology. This review highlights successes in the area with an emphasis on new opportunities and technological advances.

Synthesis of methoxylated goniothalamin, aza-goniothalamin and γ-pyrones and their in vitro evaluation against human cancer cells.

The present work describes the preparation of three novel series of compounds based on the structure of goniothalamin, a natural styryl lactone which has been found to display cytotoxic and antiproliferative activities against a variety of cancer cell lines. A focused library of 29 novel goniothalamin analogues was prepared and evaluated against seven human cancer cell lines. While the γ-pyrones and the aza-goniothalamin analogues were less potent than the lead compound, 2,4-dimethoxy analogue 88 has shown to be more potent in vitro than goniothalamin against all cancer cell lines evaluated.

Efficient Heck arylations of cyclic and acyclic acrylate derivatives using arenediazonium tetrafluoroborates. A new synthesis of the antidepressant drug (+/-)-paroxetine.

[reaction: see text] The Heck arylation of acyclic- and cyclic-substituted acrylates using several arenediazonium tetrafluoroborates was investigated. Arylations were carried out under aerobic, ligand-free conditions to provide the corresponding substituted acrylates in moderate to high isolated yields. Heck arylations were usually completed in less than 2 h in refluxing methanol.