Sven Claessens

Pyridinium Ylids in Heterocyclic Synthesis

Pyridinium ylids are versatile tools in organic synthesis. The stability of pyridinium ylids and their generation is commented. This review gives an overview of the possible modes through which pyridinium ylids can react. It is demonstrated that pyridinium ylids are suitable building blocks for the synthesis of indolizines, cyclopropanes, 2,3-dihydrofurans, 2(1H)-pyridin(ethio)ones, mono- & oligopyridines, pyranonaphthoquinones, nitrones and azepines.

Synthesis of the natural products 3-hydroxymollugin and 3-methoxymollugin.

3-Hydroxymollugin 2 and 3-methoxymollugin 3 are cytotoxic compounds isolated as minor compounds from Pentas longiflora and Rubia cordifolia. Syntheses of 3-hydroxymollugin 2 and 3-methoxymollugin 3 were developed starting from easily available 3-bromomollugin 6. Surprisingly, it was found that the reaction of 3-bromomollugin 6 with sodium methoxide in methanol resulted in the formation of 3-methoxymollugin 3 and the ring-contracted methyl isopropenylfuromollugin 7. A mechanism for this ring contraction is proposed on the basis of a pericyclic retro oxa-6pi ring-opening reaction. A second synthesis of 3-hydroxymollugin 2 was based on epoxidation of methyl 3-(3-methylbut-2-enyl)-1,4-naphthoquinone-2-carboxylate 17 and subsequent reduction of the quinone moiety, ring transformation, and DDQ oxidation. The latter oxidation process results in 3-hydroxymollugin 2 along with the rearranged furomollugin 4, which is a ring-contracted analogue of the natural product mollugin 1.

Synthesis of Benzo[f]isoindole-4,9-diones

A synthesis of benzo[f]isoindole-4,9-diones 1 is presented starting from the reaction of 2,3-bis(bromomethyl)-1,4-dimethoxynaphthalene 15 with primary amines affording 2,3-bis(aminomethyl)-1,4-dimethoxynaphthalenes 14, which could be converted by CAN-mediated oxidation in one step to benzo[f]isoindole-4,9-diones 1. An alternative synthesis of benzo[f]isoindole-4,9-diones 1 starts from 2,3-bis(bromomethyl)-1,4-naphthoquinone 9 via 2,3-dihydrobenzo[f]isoindoles 10 which spontaneously oxidize.

Synthesis of naturally occurring naphthoquinone epoxides and application in the synthesis of β-lapachone

Optimized epoxidation conditions of mono- and dialkylated naphthoquinones are presented. Based on the epoxidation protocol making use of H(2)O(2)/Na(2)CO(3), naphthoquinone epoxides are obtained in high yields. The optimized epoxidation conditions are applied in a short and high yielding synthesis of the pharmaceutically important beta-lapachone.

Efficient synthesis of cis- and trans-3,4-dihydroxy-3,4-dihydromollugin

An efficient synthesis of naturally occurring compounds isolated from Pentas longiflora, cis-3,4-dihydroxy-3,4-dihydromollugin 2, and trans-3,4-dihydroxy-3,4-dihydromollugin 3 is described. The O-protected mollugins were dihydroxylated using OsO4 to achieve the corresponding cis-dihydroxy derivatives in excellent yield. The synthesis of trans-3,4-dihydroxy-3,4-dihydromollugin was achieved using Oxone in good yield. A mechanism for the formation of cis-3,4-dihydroxymollugin acetonide from the reaction of mollugin with Oxone is proposed.

High molar mass segmented macromolecular architectures by nitroxide mediated polymerisation

A straightforward synthetic pathway based on nitroxide mediated polymerisation (NMP) for the synthesis of a variety of high molar mass segmented copolymers comprising both polystyrene (PS) and polyether segments is reported. First, various precursors such as linear or star-shaped polyether macromonomers, containing either α-methylstyrene or styrene functions at one polymer terminus, as well as PS and polyether macroalkoxyamines bearing either 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or N-tert-butyl-1-diethylphosphono-2,2-dimethylpropyl nitroxide (SG1) end-groups, were prepared. In a second step, these prepolymers were used to design different copolymer architectures such as block, graft, star-grafted, toothbrush and palm tree structures, in which PS constituted the backbone and polyether the side chains. Block copolymers were obtained by NMP of styrene initiated with polyether macroalkoxyamines. Copolymerisation of styrene with linear and star-shaped polyether macromonomers by NMP resulted in graft and star-grafted copolymers, respectively. A toothbrush copolymer was produced in a similar way with the exception of the initiator, which was a PS macroalkoxyamine. Likewise, palm tree architectures were obtained by homopolymerising polyether macromonomers initiated by PS macroinitiators. Advanced characterisation of the different polymer structures was performed, including 2D chromatography.

Synthesis of natural pyranonaphthoquinones and related antibiotic aza-analogues*

Pentalongin, the active principle isolated from the roots of the Central East African medicinal plant Pentas longiflora, revealing the basic skeleton of 3,4-dehydropyranonaphthoquinones, was synthesized by ring-closing metathesis of a suitable precursor. Mollugin, together with the (+)-cis-dihydroxylated analogue and the tetracyclic isagarin have been isolated from P. longiflora as well as from other rubiaceous herbs, which are often used in Chinese folk medicine. Synthetic routes of these natural products are presented, as well as the first syntheses of the natural products 3-hydroxy- and 3-methoxymollugin. Although pyranonaphthoquinones represent a large class of natural products, reports of their naturally occurring 2-aza analogues, all of which have been isolated as 2-aza-anthraquinones, are scarce in the literature. Nevertheless, this class of compounds has been found to possess interesting antitumor, antifungal, and antibiotic properties. Therefore, several synthetic routes to new classes of 2-aza-anthraquinones were developed. In vitro testing of the obtained compounds for their activity against Mycobacterium tuberculosis showed promising results.

Infrastructure for collaborating data-researchers in a Smart Grid pilot

A large amount of stakeholders are often involved in Smart Grid projects. Each partner has its own way of storing, representing and accessing its data. An integrated data storage and a joint online analytical mining infrastructure is needed to limit the amount of duplicated work and to raise the overall security of the system. The proposed infrastructure is composed of standard application software and an in-house developed data analysis tool that allows researchers to add and share their own functionality without compromising security.