Carlos F. Marcos

Sequential five-component synthesis of spiropyrrolidinochromanones.

Herein we report a novel, diastereoselective, one-pot, two-step, sequential synthesis of highly functionalized natural product-like spiropyrrolidinochromanones. The process consists of an Ugi four-component condensation of 3-formylchromones with amines, isocyanides, and glyoxylic acids followed by a nucleophilic conjugate addition and intramolecular cyclization. The experimental simplicity and tolerance to a wide variety of substituents makes this method suitable for combinatorial synthesis.

Synthesis of poly-ferrocene heterocycles by cycloaddition of mono- or bis(ferrocenecarbonyl)acetylenes and bis[1,2]dithiolo[1,4]thiazinethiones

Cycloaddition of a bis[1,2]dithiolo[1,4]thiazine ketothione and mono- or bis(ferrocenecarbonyl)acetylenes under catalysis by scandium triflate gave mono- and bis-ferrocenecarbonyl-1,3-dithiolylidene[1,2]dithiolo[1,4]thiazines. Cycloaddition of a bis-dithiolothiazine dithione and bis-ferrocenylbutynedione gave 3,5-di(bis-ferrocenecarbonyl-1,3-dithiolylidene)[1,4]thiazine, a structure related to extended tetrathiafulvalenes

Glu-256 is a main structural determinant for oligomerisation of human arginase I.

One determinant that could play a role in the quaternary structure of human arginase is the pair of salt links between the strictly conserved residues R255 from one monomer and E256 from every adjacent subunit. In this work, the ionic interaction between monomers was disrupted by expressing a human arginase where Glu‐256 had been substituted by Gln. Biochemical analyses of the mutant protein showed that: (i) it shares the wild‐type kinetic parameters of the arginine substrate; (ii) E256Q arginase behaves as a monomer by gel filtration; (iii) it is drastically inactivated by dialysis in the presence of EDTA, an inhibitory effect which is reversed by addition of Mn2+; and (iv) the mutant enzyme loses thermal stability. The lack of oligomerisation for E256Q arginase and the conservation of E256 throughout evolution of the protein family suggest that this residue is involved in the quaternary structure of arginases.

Enols as Feasible Acid Components in the Ugi Condensation

Heterocyclic enols are used for the first time as acid components in an Ugi-type multicomponent condensation. For that purpose, we have chosen enols containing a Michael acceptor, in order to facilitate an irreversible rearrangement of the primary Ugi adduct. The new four-component process leads readily and efficiently to heterocyclic enamines containing at least six elements of diversity.

Zinc catalysed ester solvolysis. Application to the synthesis of tartronic acid derivatives

A novel synthesis of hydroxyglycine retropeptidic derivatives was achieved through a Passerini 3-component reaction of glyoxyl amides or esters, followed by an unprecedented environmentally benign zinc catalysed solvolysis.

A multicomponent approach to the synthesis of 1,3-dicarbonylic compounds

A general synthesis of 1,3-dicarbonylic compounds using multicomponent reactions of isocyanides is described. The process involves a Passerini three-component condensation of glyoxal derivatives, isocyanides and acetic acid, followed by metal mediated reductive or solvolytic removal of the acid component. Noteworthy, reductive deacetoxylation of Passerini glyoxylamide adducts was successfully achieved using photochemically activated SmI2. This procedure constitutes a novel convenient method for the direct synthesis of malonic retro-peptidic subunits.

Regioselective Tandem [4 + 1]-[4 + 2] Synthesis of Amino-Substituted Dihydroxanthones and Xanthones.

A highly convergent and operationally simple approach to mycotoxin-related 4-amino-substituted 1-hydroxydihydroxanthones is described. The target compounds are obtained in one pot by the multicomponent reaction of 3-carbonylchromones, isocyanides, and nonsymmetric dienophiles. The reaction, which involves a tandem [4 + 1]-[4 + 2] cycloaddition, efficiently affords a variety of both monomeric and dimeric polysubstituted dihydroxanthones structurally similar to bioactive ergochromes. Further aromatization to the corresponding xanthones is readily achieved by treatment with DBU under microwave irradiation.

One-pot synthesis and chemistry of bis[1,2]dithiolopyrroles

Hunig’s base and S 2 Cl 2 give the fused 1,4-thiazines 1 and (in the presence of formic acid) 2 and 3, each of which readily extrudes sulfur, selectively and quantitatively, to give the fused pyrroles 4, 5 and 6 respectively; at higher temperatures Hunig’s base and S 2 Cl 2 can be converted into the pyrroles in one pot, and the cycloadducts 8 and 10 are thus readily available in two steps.

Bis[1,2]dithiolo[3,4-b][4′,3′-e][1,4]thiazine-3,5-dione, a planar 1,4-thiazine

N-Benzyldiisopropylamine 1 and S2Cl2 give the N-benzylbisdithiolothiazine 2, shown by X-ray crystallography to have the typically folded tricyclic structure; 2 is debenzylated by H2SO4 to give the title compound 4 which atypically has a rare near-planar 1,4-thiazine ring, gives a blue anion in solution and does not extrude sulfur thermally.

Tertiary amine–S2Cl2 chemistry: interception of reaction intermediates

The reaction of N-(2-chloroethyl)diisopropylamine 1a with S2Cl2 allows the selective one-pot preparation of the tricyclic 4-(2-chloroethyl)bisdithiolothiazines 8 and 9 or, by addition of phosphorus pentasulfide at a late stage of the reaction, of the dithiolothiazine 6b characterised by X-ray crystallography; the chloroethyl derivative 8 is also obtained from (2-diisopropylamino)ethanethiol 1b and its disulfide 1c and S2Cl2, in a rare conversion of a thiol or disulfide into the corresponding chloro compound.