Rosa M. Ortuño

Studies on structurally simple α,β-butenolides—II: (−)-(S)-γ-hydroxymethyl-α,β-butenolide and derivatives from d-ribonolactone efficient synthesis of (−)-ranunculin

Abstract A short synthesis of the title compound, 16, from d -ribonolactone is described. Two alternative approaches differing in the timing of the CC double bond creation are used to prepare some chiral derivatives of 16. (−)-Ranunculin, a glycoside present in Ranunculaceae, has been synthesized for the first time.

Studies on structurally simple α,β-butenolides—I: New syntheses of racemic γ-hydroxymethyl-α,β-butenolide and derivatives

Abstract Exhaustive approaches to the synthesis of racemic γ-heterosubstituted γ-methyl-α,β-butenolides are presented, starting mainly from C 3 synthons (glyceraldehyde, glycidaldehyde, acrolein and 2,3-epoxypropyl ethers). Good general methods for the preparation of γ-hydroxymethyl-α,β-butenolide 2 , several of its ether derivatives, as well as of γ-bromomethyl-α,β-butenolide 5 , are given. The reactivities of these structurally simple but highly functionalized compounds, convenient synthons for more complex molecules, are preliminarily explored.

Cyclobutane-containing peptides: evaluation as novel metallocarboxypeptidase inhibitors and modelling of their mode of action.

Different types of cyclobutane-containing peptides (CBPs) were screened for the first time as ligands of metallocarboxypeptidases (MCPs). CBPs are conformationally constrained, low molecular-weight compounds which showed moderate yet selective inhibitory activity against mammalian MCPs. The most potent compound was a carboxypeptidase B inhibitor. Docked protein-ligand complexes indicated that CBPs may bind to the target proteases via electrostatic interactions and aromatic stacking to catalytically crucial residues and that the placement of functional groups seems to be assisted by the rigid CBP backbone. The easily obtainable CBPs may offer a valuable alternative in the design of novel inhibitors to disease-linked metallocarboxypeptidases like human plasma carboxypeptidase B.

Reactions of some D-ribonolactone derivatives with alkyl cuprates synthesis of (+)-eldanolide and (+)-trans-cognac lactone

Abstract Reactions of some D -ribonolactone derivatives with alkyl cuprates have been investigated in order to obtain molecules with a (4 S ,5 R )-4,5-dialkyldihydro-2(3 H )-furanone type constitution. As a direct application, (+)-eldanolide and (+)- trans -cognac lactone have been synthetized.

Self‐Assembly of Chiral trans‐Cyclobutane‐Containing β‐Dipeptides into Ordered Aggregates

Two chiral synthetic β-dipeptides have been constructed, one with two trans-cyclobutane residues and the other with one trans and one cis fragment, 1 and 2, respectively, and investigated to get insight into the non-covalent interactions responsible for their self-assembly to form ordered aggregates, as well into parameters such as their morphology and size. Experimental evidence of the formation of these assemblies was provided by spectroscopy, microscopy and X-ray diffraction experiments that suggest the formation of nanoscale helical aggregates. This process involves a conformational change in the molecules of each dipeptide with respect to the preferred conformation of the isolated molecules in solution. A high-resolution NMR spectroscopy study allowed the determination of the dynamics of the gelation process in [D(8)]toluene and the sol-gel transition temperature, which was around 270 K in this solvent at a concentration of 15 mM. NMR spectroscopy experiments also provided some information about conformational changes involved in the sol-gel transition and also suggested a different gel packing for each dipeptide. These observations have been nicely explained by computational studies. The self-assembly of the molecules has been modelled and suggested a head-to-head molecular arrangement for 1 and a head-to-tail arrangement for 2 to give helical structures corresponding to hydrogen-bonded single chains. These chains interact with one another in an antiparallel way to afford bundles, the significant geometry parameters of which fit well to the main peaks observed in wide-angle X-ray diffraction spectra of the aggregates in the solid state.

Enantioselective synthetic approaches to cyclopropane and cyclobutane β-amino acids: synthesis and structural study of a conformationally constrained β-dipeptide

Abstract Synthetic approaches to carbocyclic compounds, namely cyclopropane and cyclobutane β-amino acids, are presented. One of them is based on enzymatic desymmetrization of meso diesters, leading to the enantioselective production of cis-hemiesters, which afforded β-amino acids through Curtius rearrangements. The enantiomeric excess for the cyclobutane derivatives was 91% whereas the cyclopropanes were obtained in 63% ee. According to another strategy, an enantiomerically pure cyclopropane trans-β-amino acid, bearing a quaternary center, has been synthesized from a homochiral precursor easily available from d -glyceraldehyde. The preparation and structural investigation of the first synthesized cyclobutane containing dipeptide is also described. A hairpin-like conformation of this molecule in the solid state has been demonstrated by X-ray structural analysis, showing crystal packing induced by the presence of the rigid cyclobutane moiety and the formation of intermolecular hydrogen bonds. NMR experiments confirmed that these molecules also tend to produce aggregates in solution. On the contrary, theoretical calculations suggest that intramolecular interactions are important in the gas phase, as expected.

Enantioselective total syntheses of cyclopropane amino acids: Natural products and protein methanologs

Abstract The syntheses of (−)-allo-coronamic acid, (−)-allo-norcoronamic acid, (−)-(Z)-2,3-methanohomoserine, (−)-(Z)-2,3-methanomethionine, and (2S,3R)-Cbz-cyclo-Asp-OMe have been achieved in 45–68% overall yields from suitable intermediates derived from homochiral aminopentenoates which were obtained, in turn, from D-glyceraldehyde. The key synthetic step involves the quantitative and highly diastereoselective cyclopropanation of such precursors. The factors dealing with the control of stereoselectivity are highlighted and the main features in side-chain functionalization to the respective target molecules are discussed.

Prevalence of Eight-Membered Hydrogen-Bonded Rings in Some Bis(cyclobutane) β-Dipeptides Including Residues with Trans Stereochemistry†

Three new bis(cyclobutane) beta-dipeptides have been synthesized from appropriate derivatives of cis- and trans-2-aminocyclobutane-1-carboxylic acid, respectively. The predominance of eight-membered hydrogen-bonded rings has been manifested for (trans,trans)- and (trans,cis)-beta-dipeptides while the formation of six-membered rings is preferred for the (cis,trans)- beta-dipeptide similarly to the previously described (cis,cis)-diastereomer.

Diastereofacial selectivity in uncatalyzed Diels-Alder cycloadditions involving α,β-unsaturated esters and lactones with stereogenic centers containing oxygen functiionalities

Abstract Both experimental and theoretical studies on the Diels-Alder cycloadditions of dienophiles 1 , 2 and 3 to different dienes show that the observed diastereofacial selectivity results from a combination of electronic and steric interactions. The traditional Felkin-Anh mode is not appropriate for these cases. Several new chiral synthetic building blocks have been prepared.

Enantiomeric β-angelica lactone epoxides: their syntheses from suitable chiral precursors and their use in the preparation of blastmycinone

Abstract Syntheses of ( S )-β-angelica lactone from L -tartaric acid and ( R )-γ-hydroxy-methyl-γ-butyrolactone, 5, are reported. Alternative routes to prepare 5 from S - and R -glutamic acids and D -ribonolactone, respectively, are also presented. Epoxides derived from (R)- and ( S )-β-angelica lactones have been obtained and their use in the synthesis of both (+)- and (-)-blastmycinone, 24, has been established.