Combinatorial
Chemistry & High Throughput Screening
ISSN: 1386-2073
Combinatorial Chemistry &
High Throughput Screening
Volume 10, Number 10, December 2007
Contents
Microwaves in High Throughput Synthesis (Part 2)
Guest Editors: Antonio de la Hoz and Angel Díaz-Ortiz
Microwave Reactions Under Continuous Flow
Conditions Pp. 802-836
Ian R. Baxendale, John J. Hayward and Steven V. Ley
[Abstract]
Diversity-Oriented Synthesis and Solid-Phase Organic Synthesis
Under Controlled Microwave Heating Pp. 837-856
Wei-Min Dai and Jianyu Shi
[Abstract]
Solid-Phase and Microwave-Assisted Syntheses of 857
2,5-Diketopiperazines: Small Molecules with Great Potential
Pp. 857-876
Jennifer C. O’Neill and Helen E. Blackwell
[Abstract]
Microwave-Assisted Reactions in Heterocyclic Compounds with
Applications in Medicinal and Supramolecular Chemistry
Pp. 877-902
Antonio de la Hoz, Ángel Díaz-Ortiz, Andrés
Moreno, Ana Sanchéz-Migallón, Pilar Prieto,
José Ramón Carrillo, Ester Vázquez, Mª
Victoria Gómez and Mª Antonia Herrero
[Abstract]
Microwave-Assisted Synthesis of Bioactive Quinazolines
and Quinazolinones Pp. 903-917
Thierry Besson and Elizabeth Chosson
[Abstract]
Applications of the Combination of Microwave and Parallel
Synthesis in Medicinal Chemistry Pp. 918-932
Jesús Alcázar, Gaston Diels and Bruno Schoentjes
[Abstract]
Meet the Guest Editor Pp. 933
Abstracts
[Back to top]
Microwave Reactions Under Continuous Flow
Conditions
Ian R. Baxendale, John J. Hayward and Steven V. Ley
Microwave chemistry has already impacted significantly on
the everyday synthesis of organic molecules. The adoption
and integration of this liberating technology has permitted
a resurrection of many synthetic transformations that were
previously considered too extreme in their conditions (temperatures,
pressures, reaction times) to be synthetically useful. Furthermore,
whole arrays of additional chemical transformations have been
devised under microwave heating that allow access to more
diverse chemical architectures via more expedient
routes. Continuous flow processing of chemical intermediates
taking advantage of the unique heating mechanism and characteristics
of microwave irradiation will certainly be the next evolutionary
step forward in this area. The synergistic combination afforded
by the simultaneous application of these two core processing
tools will enhance still further the synthetic capabilities
of tomorrow’s chemists. This short review aims to highlight
the current developments and future potential offered by continuous
flow microwave mediated synthesis.
[Back to top]
Diversity-Oriented Synthesis and Solid-Phase Organic Synthesis
Under Controlled Microwave Heating
Wei-Min Dai and Jianyu Shi
Diversity-oriented organic synthesis (DOS) and solid-phase
organic synthesis (SPOS) are proven technologies for generating
small molecule libraries for chemical genetics studies. Integration
of controlled microwave heating with DOS and SPOS not only
speeds up the library preparation process but also offers
unique opportunities in tackling issues which are hardly addressed
by thermal heating. Microwave-assisted synthesis is illustrated
for (a) highly regioselective Wittig olefination of cycloalkanones
by accurate regulation of temperature; (b) tandem Wittig–IMDA
sequence toward stereochemical diversity of γ-butyrolactones;
(c) one-pot alkylation–amidation approach toward appendage
diversity through use of building blocks; and (d) one-pot
U-4CR–annulation strategy toward skeletal diversity
via careful reaction design. Microwave-assisted solid-phase
organic synthesis (MASPOS) is highlighted by incorporating
with split-pool combinatorial synthesis (SPCS) of indole sulfonamides
via a key on-resin Cu(II)- or Pd(II)-catalyzed heteroannulation
under microwave heating. Design and fabrication of a novel
diglycine-derived cat•linker are described and its role
in facilitating on-resin reaction is evaluated. A traceless
synthesis of indole sulfonamides via microwave-assisted
Cu(II)-catalyzed heteroannulation of the cat•linker-tethered
substrates is also given.
[Back to top]
Solid-Phase and Microwave-Assisted Syntheses of 2,5
Diketopiperazines: Small Molecules with Great Potential
Jennifer C. O’Neill and Helen E. Blackwell
Diketopiperazines (DKPs) are a well-known class of heterocycles
that have recently emerged as a promising biologically active
scaffold. Solid-phase organic synthesis has become an important
tool in the combinatorial exploration of these privileged
structures, expediting the synthesis and, therefore, the discovery
of active compounds. To date, certain DKPs have shown potent
activities against a range of diseases and biological phenomena,
including bacterial infections, various cancers, asthma, infertility,
premature labor, and HIV. Recent applications of solid-phase
DKP synthesis, with a particular focus on cyclative cleavage
and microwave-assisted reactions, are highlighted herein.
[Back to top]
Microwave-Assisted Reactions in Heterocyclic Compounds
with Applications in Medicinal and Supramolecular Chemistry
Antonio de la Hoz, Ángel Díaz-Ortiz,
Andrés Moreno, Ana Sanchéz-Migallón,
Pilar Prieto, José Ramón Carrillo,Ester Vázquez,
Mª Victoria Gómez and Mª Antonia Herrero
Microwave irradiation has been successfully applied in organic
chemistry. Spectacular accelerations, higher yields under
milder reaction conditions and higher product purities have
all been reported. Indeed, a number of authors have described
success in reactions that do not occur under conventional
heating and modifications in selectivity (chemo-, regio- and
stereoselectivity) have even been reported. Recent advances
in microwave-assisted combinatorial chemistry include high-speed
solid-phase and polymer-supported organic synthesis, rapid
parallel synthesis of compound libraries, and library generation
by automated sequential microwave irradiation. In addition,
new instrumentation for high-throughput microwave-assisted
synthesis continues to be developed at a steady pace. The
impressive speed combined with the unmatched control over
reaction parameters justifies the growing interest in this
application of microwave heating. In this review we highlight
our recent advances in this area, with a particular emphasis
on cycloaddition reactions of heterocyclic compounds both
with and without supports, applications in supramolecular
chemistry and the reproducibility and scalability of organic
reactions involving the use of microwave irradiation techniques.
[Back to top]
Microwave-Assisted Synthesis of Bioactive Quinazolines
and Quinazolinones
Thierry Besson and Elizabeth Chosson
This paper aims to review recent developments in the synthesis
of quinazolines and quinazolinone derivatives under conditions
that include the application of microwave heating in the ring
forming step. Recently, two reviews on the synthesis and chemistry
of natural and synthetic quinazolines and quinazolinones have
been published. This review highlights significant examples
where microwave heating has been either synthetically enabling
or has provided a key advantage over conventional thermal
methods. Wherever possible, this review will focus on chemistry
carried out using monomode systems and well-designed type
of instrumentation. The review is grouped according to the
main heterocycle types in order of increasing complexity;
commencing with quinazolines and their derivatives. The microwave-assisted
synthesis of quinazolines and quinazolinones will be classified
and based on the substitution patterns of the ring system.
Syntheses of heterocyclic systems of particular biological
or commercial interest are emphasized.
[Back to top]
Applications of the Combination of Microwave and Parallel
Synthesis in Medicinal Chemistry
Jesús Alcázar, Gaston Diels and Bruno Schoentjes
The blending of microwave heating and parallel chemistry is
a logical consequence of the significant rate enhancement
and higher product yield afforded by microwave technology
and the increase in productivity afforded by combinatorial
chemistry. For this reason, this combination has become increasingly
popular in the organic chemistry community. The current review
highlights the application of this approach as a way to increase
the rate of analogue synthesis in medicinal chemistry.
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