Highlights in the solid-phase organic synthesis of natural products and analogues

Abstract

Neste trabalho nós apresentamos uma revisão sobre a síntese em fase sólida de metabólitos secundários, tais como alcalóides, poliaminas, esteróides, terpenos e flavonóides, descritos na literatura a partir de 2000. Um número considerável de rotas sintéticas elegantes e desafiadoras, usando suportes sólidos, será discutido.In this manuscript, we disclose solid-phase organic syntheses (SPOS) of small-molecules of some secondary metabolites, such as alkaloids, polyamines, steroids, terpenes, and flavonoids, described in the literature since 2000. A number of elegant, efficient and challenging syntheses on solid support will be presented.

Microwave‐assisted Solid‐phase Synthesis of N‐substituted‐2‐aminobenzo[d][1,3] Thiazine Derivatives from a BOMBA Resin

“…For synthesizing 2‐aminobenzo[ d ][1,3]thiazine derivatives based on solid‐phase, we primarily optimized reaction conditions in solution‐phase. Solid‐phase synthesis has advantages like the simple isolation of product by filtration and excess of reagents can be used to drive the reaction to completion . However, the major drawback is that it is difficult to monitor a reaction.…”

Purity profiling of Peptide Drugs

“…The coupling-deprotection is repeated until the desired amino acid sequence has been synthesised [29]. Many advantages over the solution method exist: reaction can be automated, solubilisation problem is absent due to linking to the resin, rapid synthesis, excess of reagents are added to drive reaction to completion, and reagents and solvents are easily washed away by filtering the resin [29,32,33]. Currently, solid-phase peptide synthesis remains the most reliable pathway.…”

“…Currently, solid-phase peptide synthesis remains the most reliable pathway. However, compared to synthesis in solution, it may be difficult to adapt the solution phase chemistry to a solid-phase format, the progress of the reaction can be difficult to monitor, peptide purification is only possible after cleaving the peptide from the resin, racemisation can occur during synthesis, side chains of the amino acids need to be protected [29,33]. Several synthesis strategies are developedrelating to the choices of the resin, the protecting groups, the coupling reagents and cleavage procedure.…”

“…Classically, resins are beads of polystyrene (PS) that have been cross linked with divinyl benzene (DVB), but currently, different resins are derivatised with functional groups [29,33]. Additionally, a linker may be introduced to attach the first amino acid to the resin and minimise the influence of the resin on the synthesis.…”

Monitoring Reactions on Solid Phases with Raman Spectroscopy

“…While traditional solidphase chemistry deals with repetitive coupling reactionsw ith amino acids, nucleotides, and sugars to give peptides, nucleic acids, and oligosaccharides, respectively,m odern applications of solid-supported reactions include the development of new methods for the synthesiso f, for example, heterocycles [9][10][11] and naturalp roducts. [12][13][14] Especially for the latter purposes, monitoring of the reaction and identification of the target compounds on solid supports is of major importance.T he traditionallyu sed procedures for the identification of compounds, such as elemental analysisa nd cleavage, cause drawbacks in solid-phase chemistry duet ot he loss of material and are nowadays replaced or supplemented by new techniques for the on-beada nalysiso fr eactions. The most important methods, which offer severala dvantages such as non-destructive analysis, have been introduced with the development of gelphase NMR analysis, [15,16] the use of the magic-angle spinning technique [17,18] and 19 FNMR monitoring of reactions through introduction of fluorine linkers.…”