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Combinatorial
Chemistry & High Throughput Screening
ISSN: 1386-2073
Combinatorial Chemistry &
High Throughput Screening
Volume 10, Number 9, November 2007
Contents
Microwaves in High Throughput Synthesis (Part 1)
Guest Editors: Antonio de la Hoz and Angel Díaz-Ortiz
Editorial Pp. 733-734
Parallel Processing of Microwave-Assisted
Organic Transformations Pp. 735-750
C. Oliver Kappe and Mitra Matloobi
[Abstract]
Applications of Microwave-Assisted Proteomics in Biotechnology
Pp. 751-765
Wendy N. Sandoval, Victoria Pham, Elizabeth S. Ingle,
Peter S. Liu and Jennie R. Lill
[Abstract]
Microwave Irradiation: An Important Tool to Functionalize
Fullerenes and Carbon Nanotubes Pp. 766-782
Fernando Langa and Pilar de la Cruz
[Abstract]
Microwave-Enhanced α-Arylation
of a Protected Glycine in Water: Evaluation of 3-Phenylglycine
Derivatives as Inhibitors of the Tuberculosis Enzyme, Glutamine
Synthetase Pp. 783-789
Olof Lagerlund, Luke R. Odell, Sherry L. Mowbray, Mikael
T. Nilsson, Wojciech W. Krajewski, Anneli Nordqvist, Anders
Karlén and Mats Larhed
[Abstract]
Suzuki-Miyaura and Stille Reactions as Key Steps in
the Synthesis of Diversely Functionalized Amaryllidaceae
Alkaloid Analogs Bearing a 5,6,7,8 Tetrahydrobenzo[c,e]Azocine
Skeleton Pp. 790-801
Prasad Appukkuttan, Wim Dehaen and Erik Van der Eycken
[Abstract]
Abstracts
[Back to top]
Editorial
Microwave irradiation has become a widely accepted unconventional
energy source for performing organic reactions. Microwave
heating is very attractive for chemical applications as it
produces a rapid and volumetric heating of samples that depends
strongly on the properties of the material. In contrast, conventional
heating is slow, superficial and less dependent on the properties
of the material.
In the period following the pioneering work of Gedye and Giguere,
numerous reactions were carried out in domestic microwave
ovens due to the spectacular accelerations observed in many
cases. Reactions were performed under uncontrolled conditions
and this led to conditions that were not easily reproduced
and, in certain cases, false effects involving microwave irradiation
were described.
Microwave chemistry and its related instrumentation were developed
as a result of the efforts of many pioneers, who believed
that this technology would represent the bunsen burner of
the 21st century and provide
an alternative to conventional heating to obtain results that
are not achieveble under other conditions. In particular,
the work of Loupy in France, Strauss in Australia and Varma
in the United States are worth highlighting.
The increasing number of related publications in recent years
– particularly since 2003 – could be related to
this work and the general availability of new and reliable
microwave instrumentation in which almost all of the reaction
parameters can be controlled. At this moment, any chemical
transformation known can be performed under microwave irradiation,
at temperatures ranging from –80 to 300 ºC or more,
and this methodology can be combined with other techniques
such as, for example, photochemistry, electrochemistry and
ultrasound, or employed in conjuntion with sustainable solvents
like water and ionic liquids.
A large number of reactions and conditions have been described
in organic synthesis: cycloaddition reactions, synthesis of
radioisotopes, Fullerene chemistry, Polymers, Heterocyclic
chemistry, carbohydrates and natural products, Medicinal Chemistry,
Combinatorial Chemistry and High Throughput Chemistry,
solvent-free reactions, homogeneous and heterogeneous catalysis,
Green Chemistry and, more recently, this approach has been
extended to proteomics and biological chemistry.
Microwave-Assisted Organic Synthesis is characterised by the
rapid heating induced by the radiation, which cannot be reproduced
by classical heating. Higher yields, milder reaction conditions
and shorter reaction times can be obtained and many processes
can be improved. Indeed, even reactions that do not occur
by conventional heating can be performed using microwaves,
especially when the reaction requires the use of harsh conditions
or involves sensitive reagents and/or products.
The effect of microwave exposure results from material/wave
interactions. These effects are highly dependent on the properties
of the material and produce thermal effects (which may be
easily estimated by temperature measurements) and probably
specific (i.e., not purely thermal) effects. This selective
mode of heating sometimes produces interesting modifications
in the selectivity.
Microwave reactions are characterised by short reaction times
and by clean reactions, a factor that often simplifies the
work-up procedure. In addition, microwave systems can be easily
automated both in terms of sample preparation and analysis.
These characteristics make it the technology of choice when
High Throughput Chemistry is required. Further developments
in microwave reactors and appropriate instrumentation for
Combinatorial and High Throughput Chemistry will
in future improve the utility of microwave chemistry.
The aim of this special issue, included in two parts (Vol.
10, No. 9 and Vol. 10, No. 10),
is to show some of the most recent advances in the field of
Microwave Assisted High Throughput Chemistry. Eleven contributions
from highly prestigious research groups have been selected
to cover a wide range of applications of microwave chemistry
in this field; including Heterocycles, Fullerenes and nanotubes,
Medicinal Chemistry, Proteomics, Parallel reactions, Solid-Phase
reactions and Flow conditions.
Ángel Díaz-Ortiz
Departamento de Química Orgánica
Facultad de Química
Universidad de Castilla-La Mancha
E-13071, Ciudad Real
Spain
E-mail: Angel.Diaz@uclm.es
Antonio de la Hoz
Departamento de Química Orgánica
Facultad de Química
Universidad de Castilla-La Mancha
E-13071, Ciudad Real
Spain
E-mail: Antonio.Hoz@uclm.es
[Back to top]
Parallel Processing of Microwave-Assisted Organic
Transformations
C. Oliver Kappe and Mitra Matloobi
Microwave-assisted organic synthesis is an enabling technology
that has been exploited for a variety of applications including
medicinal chemistry/drug discovery projects where speed is
often a critical factor. In this review, applications of microwave-assisted
organic synthesis employing a parallel processing regime are
summarized. Examples include parallel synthesis in domestic
microwave ovens, the use of specialized multivessel rotors
and microtiter plates in dedicated multimode microwave reactors,
and applications of SPOT synthesis on cellulose matrices.
[Back to top]
Applications of Microwave-Assisted Proteomics in Biotechnology
Wendy N. Sandoval, Victoria Pham, Elizabeth S. Ingle,
Peter S. Liu and Jennie R. Lill
Biotechnology has recently celebrated 30 years both as
a science and as a multi-billion dollar industry. One application
of biotechnology is to use human genetic information to discover,
develop, manufacture, and commercialize bio-therapeutics.
Recombinant proteins can be produced in large quantities at
high purity. High-throughput proteomic analysis is at the
heart of the biotechnology research and development process,
and the industry is constantly striving to streamline and
automate the analytical processes involved. Microwave-assisted
proteomics has recently emerged as a tool for increasing the
bio-catalysis of several processes including tryptic digestions
[1-3] lipase selectivities [4], identification of metal-catalyzed
oxidation sites on proteins [5], identification of protein
N- and C-termini [6, 7] and enzyme catalyzed N-linked
deglycosylation [8]. Here, we explore the above mentioned
methods, and describe our experiences evaluating microwave-technology
for other common proteomic protocols including: removal of
N-terminal pyroglutamyl for antibody characterization, beta
elimination and Michael addition for identification of phosphorylation
sites on recombinant proteins and enzyme mediated O-linked
deglycosylation.
[Back to top]
Microwave Irradiation: An Important Tool to Functionalize
Fullerenes and Carbon Nanotubes
Fernando Langa and Pilar de la Cruz
Microwave irradiation is an important tool in the functionalization
of fullerenes and carbon nanotubes. These are compounds with
excellent properties that make them useful for the development
of optoelectronic organic devices. The applications of microwaves
in the chemistry of these materials are reviewed.
[Back to top]
Microwave-Enhanced α-Arylation
of a Protected Glycine in Water: Evaluation of 3-Phenylglycine
Derivatives as Inhibitors of the Tuberculosis Enzyme, Glutamine
Synthetase
Olof Lagerlund, Luke R. Odell, Sherry L. Mowbray, Mikael
T. Nilsson, Wojciech W. Krajewski, Anneli Nordqvist, Anders
Karlén and Mats Larhed
A microwave-enhanced, palladium-catalyzed protocol for
the α-arylation
of a protected glycine in neat water is described. This reaction
proceeds rapidly, under non-inert conditions, to afford a
range of phenylglycine derivatives in moderate to good yields.
Based on this α-arylation,
a number of aryl L-methionine-SR-sulfoximine (MSO)
analogues were prepared and evaluated for their Mycobacterium
tuberculosis glutamine synthetase (TB-GS) inhibitory
activity.
[Back to top]
Suzuki-Miyaura and Stille Reactions as Key Steps in the Synthesis
of Diversely Functionalized Amaryllidaceae Alkaloid
Analogs Bearing a 5,6,7,8 Tetrahydrobenzo[c,e]Azocine
Skeleton
Prasad Appukkuttan, Wim Dehaen and Erik Van der Eycken
Microwave-assisted Suzuki-Miyaura and Stille cross-coupling
reactions for the synthesis of highly electron-rich and diversely
functionalized biaryl intermediates are presented. Microwave-irradiation
has been demonstrated to be a very powerful tool for performing
difficult transition metal-catalyzed cross-coupling reactions
with unfavorably substituted coupling partners. The key biaryl
intermediates were used for the microwave-enhanced construction
of the 5,6,7,8-tetrahydrobenzo[c,e]azocine skeleton
of the Apogalanthamine analogs. The success of the strategy
is demonstrated by synthesizing a number of hitherto unknown,
diversely functionalized, natural product analogs.
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