An efficient methodology for a solid phase synthesis of D- and L-cycloserine derivatives is described. Fmoc-D-cycloserine
4 and its L-enantiomer
5 prepared by a selective amine acylation of
...bis-silylated parent compounds are immobilized on Sasrin or 2-chlorotrityl linker resins using Mitsunobu-type reaction or direct tritylation, respectively. The resulting Fmoc-cycloserine resins
7, 10, and
11 are deprotected with piperidine in DMF or DCM to generate immobilized cycloserine reagents with a primary amino group exposed for various synthetic transformations. An example of the parallel D-cycloserine library synthesis on a reaction plate is described.
The first solid phase synthesis of D- and L-cycloserine derivatives is described. The method has been extended to preparation of diverse cycloserine natural product derivatives and combinatorial libraries thereof.
The chemistry of organoelement compounds is now one of the most rapidly developing fields of research, regarding both fundamental science and solution of applied problems. This review covers a ...variety of classes of organoelement compounds, ranging from molecules with highly labile carbon-element bonds to compounds with stable bonds that form the basis of novel structural materials and demonstrates their role in scientific research and industrial production. The use of Grignard reagents in modern organic synthesis and application of catalytic cyclomagnesiation and cycloalumination reactions for the preparation of difficult-to-access metallacycles are considered. The electron transfer processes in redox-active derivatives of Group 14 elements and the role of radical ions in these processes are discussed. Considerable attention is paid to organometallic compounds, first of all, as catalysts; the dynamic nature of catalysis with these compounds is noted. Unusual strained metallacycles of high thermal stability, zirconacyclocumulenes, which also exhibit catalytic activity, are described. Complexes with redox-active ligands that substantially affect the reactivity of the metal centre and directly participate in reactions with various substrates as well as organometallic compounds of lanthanides are considered. Modern environmentally benign methods for the synthesis of organosilicon compounds and production of unique materials based on them are discussed. Particular Sections are devoted to organophosphorus compounds, including those exhibiting therapeutic properties and possessing unusual optical characteristics, and organic chalcogen compounds, which find use as ligands and biologically active molecules. The bibliography includes 1045 references.
Solid-phase synthesis of a 300-member pharmacophore library of 1,4-dihydropyridines from keto ester, diketone and aldehyde building blocks on a cleavable amine polymeric support is described. ...Screening and serial deconvolution of the combinatorial library has resulted in identification of known and new potent calcium channel blockers.
A strategic analysis of various issues which pertain to the enablement of combinatorial organic synthesis to produce libraries of non-polymeric organic molecules is given. Methods and examples of the ...development of solid-phase organic chemistry and its subsequent application to combinatorial library synthesis for drug discovery is illustrated with successful case studies. The synthetic versatility of resin-bound amino-acid-derived imine intermediates to produces, ?-sultams and pyridines is shown. Use of natural products as key components for creation of combinatorial libraries is presented using Rauwolfia alkaloids and the cephalosporin nucleus as examples.
