Convertible Isonitrile Research Articles

Total Synthesis of Cordyheptapeptide A

The first total synthesis of cordyheptapeptide A is described. The synthesis is accomplished by a convergent approach featuring a combination of peptide coupling and the Ugi reaction for the preparation of the main building blocks and the acyclic precursor. The assembly of an N-methylated fragment by the Ugi reaction comprised the utilization of a convertible isonitrile followed by activation of the C-terminal amide. Two different macrocyclization sites were evaluated, proving greater efficacy the macrolactamization at the site Ile-Tyr, likely due of a more suitable conformational bias of the acyclic precursor having an internal β-turn centered at the N-Me-d-Phe-Pro moiety.

ChemInform Abstract: Synthesis of Vinyl Isocyanides and Development of a Convertible Isonitrile.

AbstractThe Wittig reaction of isocyanomethylenetriphenylphosphorane, in situ generated from the corresponding phosphonium salts, with various aldehydes affords vinyl isocyanides with good to high yields.

Synthesis of Vinyl Isocyanides and Development of a Convertible Isonitrile.

The reaction of isocyanomethylenetriphenylphosphorane, generated in situ from the corresponding phosphonium salt, with a diverse set of aldehydes afforded vinyl isocyanides in good to high yields. Excellent E-selectivity was observed for aliphatic aldehydes and 2,6-disubstituted aromatic aldehydes, whereas Z-olefins were formed predominantly with ortho-substituted aryl aldehydes. (Z)-1-Bromo-2-(2-isocyanovinyl)benzene (5l) was found to be a truly universal isonitrile since, after Ugi reaction, the resulting secondary amide unit (RNHCO-) is convertible under both acidic and basic conditions. The application of 5l in the synthesis of polyheterocycles is also illustrated.

Expedient synthesis of substituted 4-hydroxy-quinolin-2(1H)-ones

Various substituted 4-hydroxy-quinolin-2(1H)-ones were prepared in two steps via a multicomponent Ugi condensation followed by a Dieckmann cyclisation. The method was extended to the use of a convertible isonitrile to allow subsequent transformation of the amide functionality to the corresponding ester or carboxylic acid.

4-Isocyanopermethylbutane-1,1,3-triol (IPB): a convertible isonitrile for multicomponent reactions

The synthesis and applications of 4-isocyanopermethylbutane-1,1,3-triol (IPB) as a new convertible isonitrile (isocyanide) for isocyanide-based multicomponent reactions (IMCRs) like Ugi, Ugi-Smiles, and Passerini reactions are described. The primary products obtained from these IMCRs can be converted into highly activated N-acylpyrroles, which upon treatment with nucleophiles can be transformed into carboxylic acids, esters, amides, alcohols, and olefins. In this sense the reagent can be seen as a neutral carbanion equivalent to formate (HO2C−), and carboxylates or carboxamides etc. (RNu-CO−).

Ugi-4-Component Reaction Enabling Rapid Access to the Core Fragment of Massadine

A rapid method to access the densely functionalized core structure of massadine (1) has been developed. The use of the Ugi-4-component reaction involving a convertible isonitrile and an end-group differentiating ozonolysis constitute the key operations toward the synthesis of the D-ring subunit.

Facile Procedure for Generating Side Chain Functionalized Poly(α-hydroxy acid) Copolymers from Aldehydes via a Versatile Passerini-Type Condensation

A general method for synthesizing alpha-hydroxy N-acylindoles in one-pot via an acid-catalyzed condensation of a convertible isonitrile with water and various aldehydes is presented. These intermediates were incorporated into poly(alpha-hydroxy acid) copolymers bearing residues with functionalizable side chains, which could be further modified through Cu(I)-catalyzed azide-alkyne cylcoaddition reactions. This versatile synthetic strategy provides access to side chain functionalized poly(alpha-hydroxy acid) copolymers from readily available aldehydes, making it potentially useful as an approach to synthesize biodegradable polymers with new, tunable properties.

Towards molecular diversity: dealkylation of tert-butyl amine in Ugi-type multicomponent reaction product establishes tert-butyl isocyanide as a useful convertible isonitrile

With the development of a novel microwave-assisted one-pot tandem de-tert-butylation of tert-butyl amine in an Ugi-type multicomponent reaction product, tert-butyl isocyanide as a useful convertible isonitrile has been explored for the first time affording access to molecular diversity of pharmaceutically-important polycyclic N-fused imidazo-heterocycles.

Rapid Access to N-Substituted Diketopiperazines by One-Pot Ugi-4CR/Deprotection+Activation/Cyclization (UDAC)

The most efficient diversity generating approaches to heterocycles are combinations of a multicomponent (MCR) with a cyclization reaction, for example, by Ugi-deprotection-cylization (UDC) protocols. If the desired post-Ugi reaction requires more than one deprotection, for example of two initially protected Ugi-reactive groups, or if it requires additional activation, for example, by an Ugi-activation-cyclization (UAC), either the isolation of intermediates or a sequential process or both become necessary. A recently introduced convertible isonitrile reagent allows a mild and chemoselective in situ post-Ugi activation of the isonitrile-born carboxylate with simultaneous deprotection of the nucleophilic amine, that is, liberation and activation of two Ugi-reactive groups, if desired also under subsequent lactam formation. This is exemplified by the synthesis of peptide-peptoid diketopiperazines.

Application of the Ugi Reaction for the One-Pot Synthesis of Uracil Polyoxin C Analogues

A simple, two-step synthesis of amide derivatives of uracil polyoxin C (UPOC) methyl ester using the Ugi reaction is described. The four components employed in the Ugi reaction are 2',3'-isopropylidine-protected uridine-5'-aldehyde, 2,4-dimethoxybenzylamine, an isoxazolecarboxylic acid, and the convertible isonitrile N-(2-{[(tert-butyldimethylsilyl)oxy]methyl}phenyl)carbonitrile. Following the Ugi reaction, treatment with HCl in MeOH achieves deprotection of the isopropylidene group and the N-benzyl group and conversion of the isonitrile-derived amide (the Ugi product) into the corresponding methyl ester. The procedure is amenable to automated multiparallel synthesis of novel compounds related to the polyoxin and nikkomycin nucleoside-peptide antibiotics.

ChemInform Abstract: A Stable, Convertible Isonitrile as a Formic Acid Carbanion [‐COOH] Equivalent and Its Application in Multicomponent Reactions.

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: A Versatile Synthesis of α‐Amino Acid Derivatives via the Ugi Four‐Component Condensation with a Novel Convertible Isonitrile.

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A Stable, Convertible Isonitrile as a Formic Acid Carbanion [-COOH] Equivalent and Its Application in Multicomponent Reactions

Correction to: A Stable, Convertible Isonitrile as a Formic Acid Carbanion [-COOH] Equivalent and Its Application in Multicomponent ReactionsSynlett 2007; 2007(20): 3188-3192DOI: 10.1055/s-2007-990912

A Stable, Convertible Isonitrile as a Formic Acid Carbanion [-COOH] Equivalent and Its Application in Multicomponent Reactions

Corrected by: A Stable, Convertible Isonitrile as a Formic Acid Carbanion [-COOH] Equivalent and Its Application in Multicomponent ReactionsSynlett 2007; 2007(20): e3-e3DOI: 10.1055/s-2007-990941

A Versatile Synthesis of a-Amino Acid Derivatives via the Ugi Four-Component Condensation with a Novel Convertible Isonitrile

The Ugi four-component condensation (4CC) reaction with the carbonate-type isonitrile 9 proceeded smoothly, and subsequent base treatment of the Ugi products 10 provided the N-acyloxazolidinones 11 in high yield. The N-acyloxazolidinone derivatives can be reacted with several hetero-nucleophiles, namely, reaction of 11 with thiolates gave thiol ester derivatives 16 efficiently.

A Versatile Synthesis of α‐Amino Acid Derivatives via the Ugi Four‐Component Condensation with a Novel Convertible Isonitrile.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Versatile Synthesis of α-Amino Acid Derivatives via the Ugi Four-­Component Condensation with a Novel Convertible Isonitrile

The Ugi four-component condensation (4CC) reaction with the carbonate-type isonitrile 9 proceeded smoothly, and subsequent base treatment of the Ugi products 10 provided the N-acyloxazolidinones 11 in high yield. The N-acyloxazolidinones derivatives can be reacted with several hetero-nucleophiles, namely, reaction of 11 with thiolates gave thiol ester derivatives 16 efficiently.

A new resin-bound universal isonitrile for the Ugi 4CC reaction: preparation and applications to the synthesis of 2,5-diketopiperazines and 1,4-benzodiazepine-2,5-diones.

[reaction: see text] The preparation and synthetic applications of a novel resin-bound isonitrile are described. The resin is an example of a novel convertible isonitrile that can be utilized in the Ugi multicomponent reaction. Base-activation of the resin-bound Ugi product results in cleavage via formation of a N-acyloxazolidone that is then trapped as a carboxylic acid ester. This resin and the methodology described are suitable for synthesizing diversity libraries of 2,5-diketopiperazines and 1,4-benzodiazepine-2,5-diones.

Novel applications of convertible isonitriles for the synthesis of mono and bicyclic γ-lactams via a UDC strategy

This communication reveals a novel application of the so-called convertible isonitriles for the solution/solid phase generation of γ-lactam analogues. Use of tethered N-BOC aldehydes in the Ugi multi-component reaction (MCR), followed by BOC removal and base treatment (a ‘3-step, 1-pot procedure’) affords γ-lactams in good yield. The UDC (Ugi/De-BOC/Cyclize) strategy, coupled with a convertible isonitrile, is now feasible from all three substitution sites of the Ugi product. A conceptually novel approach, combining a bi-functional precursor with a post-condensation modification to give fused lactam-ketopiperazines, is also revealed.

ChemInform Abstract: Improved Procedure for the Solution Phase Preparation of 1,4‐Benzodiazepine‐2,5‐dione Libraries via Armstrong′s Convertible Isonitrile and the Ugi Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.