John A. Porco

Pestacin: a 1,3-dihydro isobenzofuran from Pestalotiopsis microspora possessing antioxidant and antimycotic activities

Abstract Pestalotiopsis microspora, an endophytic fungus native to the rainforest of Papua New Guinea, produces a 1,3-dihydro isobenzofuran. This product, pestacin, is 1,5,7-trisubstituted and exhibits moderate antifungal properties and antioxidant activity 11 times greater than the vitamin E derivative trolox. Antioxidant activity is proposed to arise primarily via cleavage of an unusually reactive C–H bond and, to a lesser extent, through O–H abstraction. Isolation of pestacin was achieved by extraction of culture fluid with methylene chloride followed by silica gel chromatography. Structure was established by X-ray diffraction and 13C and 1H NMR. The X-ray data demonstrate that pestacin occurs naturally as a racemic mixture. A mechanism for post-biosynthetic racemization is proposed.

Polycyclic xanthone natural products: structure, biological activity and chemical synthesis

Polycyclic xanthone natural products are a family of polyketides which are characterized by highly oxygenated, angular hexacyclic frameworks. In the last decade, this novel class of molecules has attracted noticeable attention from the synthetic and biological communities due to emerging reports of their potential use as antitumour agents. The aim of this article is to highlight the most recent developments of this subset of the xanthone family by detailing the innate challenges of the construction of this class of natural products, new synthetic approaches, and pharmacological data.

Synthetic cyclohexenyl chalcone natural products possess cytotoxic activities against prostate cancer cells and inhibit cysteine cathepsins in vitro.

A number of cyclohexenyl chalcone Diels-Alder natural products possess promising biological properties including strong cytotoxicity in various human cancer cells. Herein, we show that natural products in this class including panduratin A and nicolaioidesin C inhibit cysteine cathepsins as indicated by protease profiling assays and cell-free cathepsin L enzyme assays. Owing to the critical roles of cathepsins in the biology of human tumor progression, invasion, and metastasis, these findings should pave the way for development of novel antitumor agents for use in clinical settings.

Organic synthesis using chemical tags: the third Leg of parallel synthesis.

Increasing emphasis has recently been placed on the development of synthetic methods which effectively couple chemical synthesis and purification. For example, new formats for parallel synthesis are being developed which involve attachment of chemical tags to both reagents, reactants, and substrates to permit their chemoselective removal from reaction mixtures. The driving force for the development of tagged organic reagents is the ability to use standard solution-phase chemistry methods and reaction monitoring techniques (e.g. TLC and HPLC). In this mini-review, we will outline recent developments on the growing class of chemically tagged reagents, reactants, and substrates and highlight examples of their use in multistep synthesis.

A photochemical flow reactor for large scale syntheses of aglain and rocaglate natural product analogues

Herein, we report the development of continuous flow photoreactors for large scale ESIPT-mediated [3+2]-photocycloaddition of 2-(p-methoxyphenyl)-3-hydroxyflavone and cinnamate-derived dipolarophiles. These reactors can be efficiently numbered up to increase throughput two orders of magnitude greater than the corresponding batch reactions.

Eucalyptusdimers A–C, Dimeric Phloroglucinol–Phellandrene Meroterpenoids from Eucalyptus robusta

Eucalyptusdimers A-C, three dimeric phellandrene-derived meroterpenoids featuring an unprecedented, fused skeleton between two phellandrene and two acylphloroglucinol subunits, along with one biogenetically related intermediate, (±)-eucalyprobusone A, were isolated from the fruits of Eucalyptus robusta. Their structures and absolute configurations were elucidated using spectroscopic data, X-ray crystallography, and electronic circular dichroism analysis. The isolated meroterpenoids were evaluated for their anti-inflammatory, acetylcholinesterase inhibitory, and protein tyrosine phosphatase 1B inhibitory effects.

Asymmetric Dearomatization/Cyclization Enables Access to Polycyclic Chemotypes: Asymmetric Dearomatization/Cyclization Enables Access to Polycyclic Chemotypes

Enantioenriched, polycyclic compounds were obtained from a simple acylphloroglucinol scaffold. Highly enantioselective dearomatization was accomplished using a Trost ligand-palladium(0) complex. A computational DFT model was developed to rationalize observed enantioselectivities and revealed a key reactant-ligand hydrogen bonding interaction. Dearomatized products were used in visible light-mediated photocycloadditions and oxidative free radical cyclizations to obtain novel polycyclic chemotypes including tricyclo[4.3.1.01,4]decan-10-ones, bicyclo[3.2.1]octan-8-ones and highly-substituted cycloheptanones.