Hypervalent iodine reagents have been applied in many metal-free, efficient synthesis of natural products and other bioactive compounds. In particular, treatment of alcohols, acetals and acids with hypervalent iodine reagents and iodine results in O-radicals that can undergo a β-scission reaction. Under these oxidative conditions, derivatives of amino acids, peptides or carbohydrates are converted into cationic intermediates, which can subsequently undergo inter- or intramolecular addition of nucleophiles. Most reported papers describe the addition of oxygen nucleophiles, but this review is focused on the addition of carbon, nitrogen and phosphorous nucleophiles. The resulting products (nucleoside and alkaloid analogs, unnatural amino acids, site-selectively modified peptides) are valuable intermediates or analogs of bioactive compounds.

Carbamate-bearing benzylated aminosugars undergo an I2/I(III)-promoted intramolecular hydrogen atom transfer (IHAT) followed by a nucleophilic attack to provide polycyclic structures. Thus, suitably positioned benzyl ethers are surgically oxidized into the corresponding mixed N/O-benzylidene acetals, which can be conveniently deprotected under mild acidic conditions to grant access to selectively O-deprotected aminosugars amenable for further derivatization. The scope of this strategy has been proven with a series of furanosic and pyranosic scaffolds. Preliminary mechanistic studies, including Hammett LFER and KIE analyses, support a reaction pathway with nucleophilic cyclization as the rate-determining step.

Exciting developments in the site-selective modification of peptide backbones are allowing an outstanding fine-tuning of peptide conformation, folding ability, and physico-chemical and biological properties.

The fragmentation of anomeric alkoxyl radicals (ARF) and the subsequent cyclization promoted by hypervalent iodine provide an excellent method for the synthesis of guanidino-sugars. The methodology described herein is one of the few existing general methodologies for the formation of medium-sized exo- and endoguanidine-containing heterocycles presenting a high degree of oxygenation in their structure.

Host-defense peptides, also called antimicrobial peptides (AMPs), whose protective action has been used by animals for millions of years, fulfill many requirements of the pharmaceutical industry, such as: (1) broad spectrum of activity; (2) unlike classic antibiotics, they induce very little resistance; (3) they act synergically with conventional antibiotics; (4) they neutralize endotoxins and are active in animal models. However, it is considered that many natural peptides are not suitable for drug development due to stability and biodisponibility problems, or high production costs. This review describes the efforts to overcome these problems and develop new antimicrobial drugs from these peptides or inspired by them. The discovery process of natural AMPs is discussed, as well as the development of synthetic analogs with improved pharmacological properties. The production of these compounds at acceptable costs, using different chemical and biotechnological methods, is also commented. Once these challenges are overcome, a new generation of versatile, potent and long-lasting antimicrobial drugs is expected.

The synthesis of benzimidazole-fused iminosugars through a tandem β-fragmentation-intramolecular cyclization reaction is described. The use of the benzimidazole ring as the internal nucleophile and the use of phenyliodosophthalate (PhI(Phth)), a new metal-free and low toxic hypervalent iodine reagent, are the most remarkable novelties of this synthetic strategy. With this approach, we have demonstrated the usefulness of the fragmentation of anomeric alkoxyl radicals promoted by the PhI(Phth)/I2 system for the preparation of new compounds with potential interest for both medicinal and synthetic chemists.

Due to the worrying increase in antimicrobial resistance to conventional antibiotics, the search for alternatives is becoming increasingly important. Antimicrobial peptides (AMPs), originating from natural resources, have been recognised as a novel class of antibiotics. An advantage of peptides over antibiotics is that the resistance is more difficult to attain than for conventional antibiotics. With the increasing number of genomes sequenced and available in the public domain, one alternative methodology to obtain novel AMPs is to analyse genes and proteins from genomic databases to predict and identify amino acid sequences that share similarities and molecular features with natural bioactive antimicrobial peptides. In this chapter, we summarise some of our recent results on the production of antimicrobial peptides, particularly, how we managed to identify a family of antimicrobial peptides: cathelicidins, through bioinformatics tools, from the genomes of two lower vertebrates (a reptile and a bird) available in public databases. We hope that our preliminary investigation with these novel peptides could be useful for the design of future strategies that pursue the production of antimicrobial peptides through biotechnology.

Libraries of compounds containing heteroaromatic rings and other nitrogen heterocycles were [...]

AbstractConditions A) and B) are elaborated as optimal for the preparation of pyrrolidine or 2‐pyrrolidonone structures via radical‐mediated methyl iodination/oxidative deiodination.

Mechanistic evidence observed in Hofmann-Löffler-Freytag-type reactions has been crucial to achieve the chemoselective functionalization of methyl groups under mild conditions. Radical-mediated methyl iodination and subsequent oxidative deiodination are the key steps in this functionalization, where iodine chemistry has a pivotal role on the formation of the C-N bond. The concepts of single hydrogen atom transfer (SHAT) and multiple hydrogen atom transfer (MHAT) are introduced to describe the observed chemoselectivity.

The synthesis of a novel type of branched iminosugars is described. This synthetic strategy is based on two key reactions: first, an aldol reaction with formaldehyde in order to introduce selectively the hydroxymethyl branch, and second, a tandem β-fragmentation-intramolecular cyclization reaction. The combination of both reactions afforded a battery of compounds exhibiting a great structural complexity, with the concomitant formation of a quaternary center, starting from readily available aldoses. With this approach we have demonstrated the usefulness of the fragmentation of anomeric alkoxyl radicals (ARF) promoted by the PhIO/I2 system for the preparation of new compounds with potential interest for both medicinal and synthetic chemists.

The fragmentation of anomeric alkoxyl radicals (ARF) and the subsequent intramolecular cyclization promoted by hypervalent iodine reagents provide an excellent method for the synthesis of tetrazolo-sugars. This new reaction offers additional advantages for the synthesis of these compounds, including the ready availability of the starting materials, experimental simplicity, mild conditions, and good yields.

The ability of the guanidinylating reagent N',N''-diBoc-N-triflyl-guanidine (GN-Tf) to react with in situ formed free amines from azides in carbohydrate scaffolds was explored. This reaction proved to be an efficient method to prepare guanidine derivatives in a one-pot manner with good to excellent yields, either with primary or secondary azides with different substitution patterns. Labile protecting groups such as benzyl ethers are not removed under these hydrogenolytic conditions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

1,1,1-Trihaloalkanes of the types R–CCl2I, R–CClBrI, and R–CBr2I belonging to 1,1,1-trihalo-1-deoxy-d-arabinitol series of alditols were prepared and fully characterized by anomeric alkoxyl radical fragmentation of the corresponding 2,2-dihalo-2-deoxy-d-arabino-hexopyranose derivatives. The analogous diiodohalo compounds R–CClI2 and R–CBrI2 could not be prepared by this methodology. The results strongly suggest that the stability of the mixed trihalo alditols decreases with increasing bulkiness of the halogen atoms.

The chemoselective radical reduction of the iodine atom in a series of 1-deoxy-1-halo-1-iodo-alditols with the 1-ethylpiperidine hypophosphite (EPHP)/AIBN system is described. EPHP is also a good chain carrier for the radical addition of gem-dihalocompounds to electron-deficient olefins. Thus, the synthesis of 4-halo-glycooctononitriles and 4-halo-glycoheptononitriles can be achieved by an intermolecular addition of the 1-deoxy-1-halo-alditol-1-yl radical intermediate to acrylonitrile.

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AbstractFor Abstract see ChemInform Abstract in Full Text.