Giordano Lesma

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A dynamic combinatorial library of thiocolchicine-podophyllotoxin derivatives based on the disulfide bond exchange reaction is described. The influence of a biological target on the composition of the reaction mixture has been demonstrated. Use of high-resolution ESI mass spectrometry to evaluate the composition of the mixture shows promise for the design(More)
Herein we report on the multicomponent synthesis of a novel imidazole-based compound, able to act efficiently as a minimalist β-strand mimic. Biological evaluation proved its ability to impair the LDLR-PCSK9 protein-protein interaction, disclosing it as the first small molecule exerting a PCSK9-mediated hypocholesterolemic effect.
We present here spirocyclic lactam derivatives, embodying D-Phe and L-Ala amino acids as the central core and acting as tetrapeptide and hexapeptide mimetics. An efficient route for their synthesis is demonstrated by using the strategic combination of Seebach's self-reproduction of chirality chemistry and the Pictet-Spengler condensation as key steps. The(More)
trans-6-Aminocyclohept-3-enols 18 and ent-18 are new designed polyfunctionalized chiral building blocks for piperidine alkaloids synthesis and are prepared in high yields from the enzymatically derived cyclohept-3-ene-1,6-diol monoacetate (-)-8. Efficient highly enantioselective syntheses of cis-4-hydroxypipecolic acid (1) and piperidines 3 and 4, in both(More)
Kinetic resolution of N-Boc-piperidine-2-ethanol (2), a case of remote stereocenter discrimination, was accomplished by sequential transesterification mediated by two enzymes, Lipase PS and porcine pancreatic lipase, showing opposite enantioselectivity. The gram-scale availability of the two enantiomeric N-Boc alcohols 2a (R) and 2c (S) enlarges their(More)
We report here a two step efficient route for the synthesis of 1,2,3,4-tetrahydro-β-carboline (THBC)-based tetracyclic peptidomimetics from a Ugi 4-CR/Pictet-Spengler reaction sequence. Suitably N-protected 2-aminoacetaldehyde was for the first time applied as the carbonyl component in a Ugi four-component reaction, opening the way to the employment of(More)
This study reports on our ongoing investigation on hybrid EM-2 analogues, in which the great potential of β-amino acids was exploited to generate multiple conformational modifications at the key positions 3 and 4 of the parent peptide. The effect on the opioid binding affinity was evaluated, by means of ligand stimulated binding assays, which indicated a(More)
The synthesis of a novel Phe-Ala dipeptide mimic, built up on a diazaspirocyclic lactam core, is presented. This new scaffold was evaluated for conformational mimicry of reverse turn by combining molecular modeling, IR, NMR, and X-ray diffraction experiments. All these tools agree on the presence of a strong intramolecular hydrogen bond, thus demonstrating(More)
An efficient Ugi three-component reaction of a preformed chiral ketimine derived from isatin with various isonitrile and acid components has been developed. The reactions proceeded smoothly and in a stereocontrolled manner with regard to the new center of the Ugi products due to the stereoinduction of the amine chiral residue. A wide variety of novel chiral(More)
The irradiation of colchicone 5 led to the formation of lumicolchicone 7. The same reaction cannot be obtained by using thiocolchicone 6 as substrate. Transient absorption spectroscopy of colchicone and beta-lumicolchicone showed that probably the photoisomerization occurred on colchicone in its first excited singlet state. The spectroscopic data are in(More)