Facile solid-phase synthesis of biotinylated alkyl thiols
Elisabet Prats‐AlfonsoFayna García‐MartínNúria Bayó‐PuxánLuis J. CruzMateu Pla‐RocaJosep SamitierAbdelhamid ErrachidFernando Alberício
20
Citation
22
Reference
10
Related Paper
Citation Trend
Keywords:
Solid-Phase Synthesis
Traceless solid-phase synthesis represents an ultimate sophisticated synthetic strategy on insoluble supports. Compounds synthesized on solid supports can be released without a trace of the linker that was used to tether the intermediates during the synthesis. Thus, the target products are composed only of the components (atoms, functional groups) inherent to the target core structure. A wide variety of synthetic strategies have been developed to prepare products in a traceless manner, and this review is dedicated to all aspects of traceless solid-phase organic synthesis. Importantly, the synthesis does not need to be carried out on a linker designed for traceless synthesis; most of the synthetic approaches described herein were developed using standard, commercially available linkers (originally devised for solid-phase peptide synthesis). The type of structure prepared in a traceless fashion is not restricted. The individual synthetic approaches are divided into eight sections, each devoted to a different methodology for traceless synthesis. Each section consists of a brief outline of the synthetic strategy followed by a description of individual reported syntheses.
Solid-Phase Synthesis
Linker
Organic Synthesis
Peptide Synthesis
Cite
Citations (24)
Comparing a solution phase route to a solid phase route in the synthesis of the cytotoxic natural product urukthapelstatin A (Ustat A) confirmed that a solid phase method is superior. The solution phase approach was tedious and involved cyclization of a ridged heterocyclic precursor, while solid phase allowed the rapid generation of a flexible linear peptide. Cyclization of the linear peptide was facile and subsequent generation of three oxazoles located within the structure of Ustat A proved relatively straightforward. Given the ease with which the oxazole Ustat A precursor is formed via our solid phase approach, this route is amenable to rapid analog synthesis.
Oxazole
Solid-Phase Synthesis
Peptide Synthesis
Natural product
Cite
Citations (21)
Solid-Phase Synthesis
Conjugate
Cite
Citations (1)
1,2,4-Triazoles were synthesized on a solid support in three steps, with excellent yields and purities. The utility of this triazole-functionalized solid support was demonstrated by the solid-phase synthesis of various trisubstituted 1,2,4-triazoles.
Solid-Phase Synthesis
Triazole
Solid surface
1,2,4-Triazole
Cite
Citations (36)
Solid-Phase Synthesis
Cite
Citations (2)
In this account dedicated to '100 years Roche' in CHIMIA, we present some of our strategies towards the synthesis of interesting novel amino-acid-derived building blocks; multigeneration synthesis of thiazole libraries in solution; a novel solid-phase approach towards highly substituted pyrimidines using a novel safety-catch linker principle and a multidirectional cleavage procedure; a versatile solid-phase synthesis of quinazolones taking advantage of the Staudinger phosphorylimine chemistry combined with a novel cyclization and cleavage strategy, and finally a novel solid-phase diketopiperazine synthesis combining the Ugi four-component reaction with a final ring-forming cleavage step.
Solid-Phase Synthesis
Cleavage (geology)
Linker
Thiazole
Combinatorial synthesis
Cite
Citations (70)
Many synthetic routes have been explored to make small molecule sulfonimidamides (SIAs), however, its introduction into larger molecules such as oligopeptides has not been studied before. We herein demonstrate three alternative and complementary methods for synthesis of SIA based pseudopeptides, on solid phase, using both on and off‐resin SIA‐synthesis, via sulfonimidoyl chlorides from sulfonamides, in high conversion. Beside evaluation of various resins such as 2‐CTC, Wang, and Rink amide‐ChemMatrix, the possibilities to further N ‐functionalize and cyclize the SIA functionality on solid support are shown. The diastereomers of SIA containing pseudopeptides could in most cases be separated using normal reverse phase preparative HPLC. The solid phase SIA methodology has many advantages when it comes to handling and purification as compared to in solution, and will therefore enable exploration of the SIA group as isosteric substitutions and peptidomimetic building blocks in the development of drug‐like pseudopeptides in many ways. Of particular note these approaches facilitate combinatorial library synthesis as demonstrated herein.
Solid-Phase Synthesis
Peptidomimetic
Combinatorial synthesis
Diastereomer
Amide
Peptide Synthesis
Cite
Citations (7)
With the rapid development of combinatorial chemistry using solid phase synthesis, there is a great deal of interest in developing new solid phase linkers, which are stable during the solid phase synthesis process and yet readily cleavable under mild conditions. By taking advantage of a "trimethyl lock"-facilitated lactonization reaction, we have developed a redox-sensitive resin linker for the synthesis of C-terminal-modified peptides. The cleavage only requires mild reducing agents such as sodium hydrosulfite, which is not expected to cause any problem with the commonly seen organic functional groups. Using this new linker, three short peptides were synthesized with high isolated yields (70-90%). Such a linker could potentially be used for the synthesis of modified peptide libraries, which allows for the ready cleavage of the linker under mild conditions.
Linker
Solid-Phase Synthesis
Cleavage (geology)
Peptide Synthesis
Cite
Citations (44)
Solid-Phase Synthesis
Wittig reaction
Sequence (biology)
Staudinger reaction
Cite
Citations (5)