Current Organic Chemistry, Volume 6, No. 15, 2002
Contents
Desymmetrisation of Cyclic Dienes. An Efficient Strategy for Natural Products Synthesis Pp.1369-1395
N.
Abd Rahman, Y. Landais
Study of the cis-trans Isomerization of the
Amino-Acyl prolyl Peptide
Bond. Application
to the Design of Novel Inhibitors of Immunophilins Pp.1397-1431
Christophe Dugave
New Perspectives for Iodine (III) Reagents in
(Hetero)Biaryl Coupling
Reactions Pp.1433-1452
I.
Organic Polycationic
Salts – Syntheses and Applications Pp.1453-1467
Robert Engel and JaimeLee Iolani Cohen
Recent Advances in the Synthesis of Optically
Active Compounds Bearing a Chiral
Toshihiro
Murafuji, Kei Kurotobi, Norihiro Nakamura,Yoshikazu Sugihara
Abstracts
[Back to top] Desymmetrisation of Cyclic Dienes. An Efficient Strategy for Natural Products Synthesis
N.
Abd Rahman, Y. Landais
Desymmetrisation processes allow a rapid and stereocontrolled elaboration of readily available s-symmetric precursors. Since it is often more
convenient to prepare symmetrical compounds, breaking the symmetry at a
well-defined point in a synthesis may constitute a powerful manner to introduce
several chiral centres with high level of diastereo- and enantiocontrol.
This review is
intended to provide the reader with a timely report on the novel synthetic
possibilities offered by desymmetrisation of some
substituted 1,3-cyclopentadienes and
1,4-cyclohexadienes. Our recent investigations in this field, mainly on silicon
derived cyclopenta- and cyclohexadienes
will be described along with reports by other groups working on closely related
precursors. The scope and limitation of this methodology will be examined. The
influence of the ring substituents on the regio- and stereochemical outcome
of the desymmetrisation processes will also be
discussed. For instance, we have demonstrated that a silicon group at the
pseudo-symmetrical position, was crucial for the
control of the diastereofacial selectivity. The discussion
will also focus on the asymmetric processes which have been used to break the
symmetry of the dienes and on the elaboration of the adducts to construct biologically relevant targets. Sharpless asymmetric dihydroxylation
and amino-hydroxylation, hydroboration and cyclopropanation are the most reliable and efficient
processes, which have been used so far. Asymmetric Heck reaction has also been
employed demonstrating that this methodology can be further enriched with new
asymmetric processes and that numerous homochiral
intermediates would be at hand in a near future. Finally, illustration of the
viability of such a strategy will be provided along with the total synthesis of
relevant classes of natural products such as cyclitols,
sugar mimics having glycosidase inhibitory activities, alkaloids and sesquiterpenes.
[Back to top] Study of the cis-trans Isomerization of the
Amino-Acyl prolyl Peptide
Bond. Application
to the Design of Novel Inhibitors of Immunophilins
Christophe Dugave
Cis-trans isomerization
of amide bonds plays a crucial role in protein structure as well as in the
activity of peptides. In particular, the amino acyl-proline
cis-trans interconversion
is one of the limiting steps of protein folding and is accelerated by a family
of proteins called immunophilins or peptidyl-prolyl isomerases (PPIases). Consequently, PPIases
are implicated in many biological processes such as protein expression, mitosis
and cellular communication. They also play a role in immunosuppression
as well as in several pathologies such as AIDS and severe neurodegenerative
disorders. Therefore, immunophilins are attractive
targets for the design of novel therapeutics. In this review, the design of
selective PPIases inhibitors will be detailed on the
basis of structural data and structure-activity realtionship
studies. The preparation and biochemical evaluation of new molecules derived
from immunosuppressive inhibitors of immunophilins
such as cyclosporin and FK506 will be tackled.
Results, collated with structural data, will then be used with view to
developing potent and selective inhibitors devoid of immunosuppressive
activity. In particular the design and synthesis of ground-state inhibitors and
non-isomerisable analogs of the amino acyl-proline moiety, including constrained proline, proline mimetics and endogenous cyclophilin
ligands, will be explained. Finally, we will focus on
the synthesis of transition-state analog inhibitors of the PPIases
including ketoamides, phosphonamides
and sulfonamides.
[Back to top] New Perspectives for Iodine (III) Reagents in
(Hetero)Biaryl Coupling
Reactions
I.
The biomimetic phenolic and non-phenolic oxidative coupling approach to the construction of
biaryl connections represents an alternative to other
known methodologies, such as Ullmann or Stille reactions, with the advantage that no functionalization at the coupling positions is required.
However, most of the reagents commonly used for oxidative bond formation are
highly toxic and environmentally harmful.
This review
focuses on the use of easily handle and less toxic hypervalent
iodine reagents phenyliodine(III)bis(trifluoroacetate)
or PIFA and phenyliodine(III)diacetate
or PIDA, to perform such a key transformation as the formation of the biaryl linkage is in Synthetic Organic Chemistry. This
methodology has been used in the synthesis of symmetric and unsymmetric
biaryl compounds in both inter- and intramolecular fashion with high yields and complete regioselectivity. Moreover, chiral
biaryl derivatives have been successfully synthesized
employing these reagents.
On the other hand,
recent results have demonstrated that a combination of the advantages shown by
this type of reagents, with those derived from solid phase organic synthesis
can be successfully applied to improve the construction of derivatives
incorporating the biaryl framework.
Finally, this methodology had not been applied to perform the synthesis of aryl-heteroaryl bonds so far. This review also summarizes our recent advances toward this end.
[Back to top] Organic Polycationic
Salts – Syntheses and Applications
Robert
Engel and JaimeLee Iolani
Cohen
Several series of polyammonium and polyphosphonium
organic salts are surveyed. These polycationic salts
may be divided into several topographical categories based upon their
structural characteristics (such as dendrimers, rings
and strings) and their physical state (solid, liquid crystalline, liquid). The
synthetic approaches and the physical/chemical characteristics for each series
are surveyed, along with their physical and chemical characteristics, including
their utility for ion exchange, their interaction with biological systems, and
their antihydrophobic effect.
[Back to top] Recent Advances in the Synthesis of Optically Active Compounds Bearing
a Chiral
Toshihiro
Murafuji, Kei Kurotobi, Norihiro Nakamura,Yoshikazu Sugihara
The design and
construction of optically active molecules comprised of a chiral
heteroatom center is a rapidly developing research field. This review focuses
on the recent development in the synthesis of such molecules which possess a chiral heteroatom center of the group 13–16 metal
elements, that is, boron, silicon, germanium, tin, arsenic, antimony, bismuth,
selenium and tellurium.