La falsificazione epigrafica. Questioni di metodo e casi di studio

This paper aims to reconsider the manuscript by Jacopo Valvasone (1499-1570), formerly owned by the Earl of Leicester (now British Library, Additional MS 49369), which Theodor Mommsen borrowed and inspected in 1876, just before the publication of the second part of CIL V. In the letter that he wrote to thank the Vicar and Librarian of Halkham Hall, Mommsen declared that Valvasone joined \u201cthe the long list of forgers\u201d. The analysis of forgeries in Valvasone\u2019s manuscript could show whether Mommsen was right in his opinion

Epoxyalcohol Route to Hydroxyethylene Dipeptide Isosteres. Stereodivergent Synthesis of the Diaminoalcohol Core of Ritonavir and its C-2 Epimer.

A stereoselective synthesis of hydroxyethylene dipeptide isosteres based on the 1,4-diamino-2- hydroxybutane structure is described. Horner-Emmons olefination of phosphonates derived from R-amino acids, stereoselective reduction of the resulting enones to allylic alcohols, and syn epoxidation of the latter lead to enantiomerically pure 1-amino-2-hydroxy-3,4-epoxybutanes, key intermediates in the synthesis. Reductive cleavage of the epoxy alcohols with Red-Al proceeds in a highly regioselective way, giving 1-amino-2,4-dihydroxybutanes, from which diamino alcohol hydroxyethylene isosteres are obtained by selective protection of the secondary 2-hydroxy group, via cyclization to 1,3-oxazolidinone, and further elaboration of the 4-hydroxy. Both C-2 epimers of 1,4-diamino-2-hydroxybutanes are accessible by appropriate choice of the conditions for cyclization. The approach is demonstrated by the synthesis of a series of six hydroxyethylene dipeptide isosteres, including the diamino alcohol core of potent HIV-protease inhibitor ritonavir 18 and its C-2 epimer 11a

L\u2019uso del protossido d\u2019azoto per la sedazione procedurale

N/

Synthesis of a val-pro diaminodiol dipeptide isostere by epoxyamine cyclization

The base-catalyzed hydroazidation of alpha'-amino alpha,beta-unsaturated ketones with in situ generated hydrazoic acid was found to proceed with highstereoselectivity in favor of the syn product. The stereoselectivity is controlled by the configuration of the enone and syn/anti ratios up to 7:1were obtained with secondary and tertiary amines at low temperature. By this route the diamino alcohol core of HIV-PR inhibitors ritonavir andlopinavir was synthesized in 37% yield from phenylalanine

Val-Ala Dipeptide Isosteres via Hydrocyanation of alfa'-Amino-alfa,beta-Unsaturated Ketones. Control of Stereoselectivity by the N-Protecting Group.

Three diastereoisomeric hydroxyethylene isosters of the Val- Ala dipeptide were synthesized from \u3b1,\u3b2-unsaturated ketones 1 derived from N-Boc- and N,N-dibenzyl-L-valine. The enones were hydrocyanated with diethylaluminum cyanide to give the corresponding \u3b2-cyano ketones with the stereoselectivity depending on the protecting group. N-Boc protected enone 1a gave a 1:1 mixture of anti and syn adducts 4a, 5a while the corresponding N,N-dibenzyl compound 1c gave a 6:1 mixture of anti, syn adducts 4c, 5c. Borohydride reduction of the resulting cyano ketones is also controlled by the protecting group, resulting in opposite stereoselectivities for N-Boc and N,N-dibenzyl compounds. The cyano alcoholsthus obtained were converted, in several steps, into two series of enantiomerically pure hydroxyethylene isosters of the Val-Ala dipeptide. In the first series the hydroxy group and the N-terminal of the isoster are internally protected through the formation of an oxazolidine; in the second series the hydroxy group and the C-terminal are protected as lactone. Two oxazolidines (28, 29), corresponding to syn,syn and syn,anti 4-hydroxy-5-amino acid isosters, and three lactones (23 1225), corresponding to syn,syn, syn,anti, and anti,anti isosters were obtained by this approach

Flexible synthesis of symmetric and non-symmetric hiv-1 protease inhibitors based on all-s-diaminodiol isosteres

C2 symmetric and non-symmetric pseudopeptide inhibitors of HIV-1 protease, containing a S,S,S,S-diaminodiol isostere have been obtained by a synthetic strategy designed to couple a high degree of stereochemical control with complete flexibility in the choice of residues in the central core and flanking chains. Using this approach, inhibitors with IC50 values in the low nanomolar range were assembled from readily available aminoacids and carboxylic acids, chosen with the aid of molecular modelling

Stereoselective synthesis of non symetric dihydroxyethylene dipeptide isosteres via epoxyalcohols derived from \u3b1-amino acids

C2 symmetric and non-symmetric pseudopeptide inhibitors of HIV-1 protease, containing a S,S,S,S-diaminodiol isostere have been obtained by a synthetic strategy designed to couple a high degree of stereochemical control with complete flexibility in the choice of residues in the central core and flanking chains. Using this approach, inhibitors with IC50 values in the low nanomolar range were assembled from readily available aminoacids and carboxylic acids, chosen with the aid of molecular modelling

Stereoselective Synthesis of non Symmetric Dihydroxyethylene Dipeptide Isosteres via Epoxyalcohols Derived from alpha-Amino Acids

6C2 symmetric and non-symmetric pseudopeptide inhibitors of HIV-1 protease, containing a S,S,S,S-diaminodiol isostere have been obtained by a synthetic strategy designed to couple a high degree of stereochemical control with complete flexibility in the choice of residues in the central core and flanking chains. Using this approach, inhibitors with IC50 values in the low nanomolar range were assembled from readily available aminoacids and carboxylic acids, chosen with the aid of molecular modelling.nonenoneF. BENEDETTI; M. MAGNAN; S. NORBEDO; D. PARAT; S. MIERTUS; TOSSI A.Benedetti, Fabio; M., Magnan; Norbedo, Stefano; D., Parat; Miertus, Stanislav; Tossi, Alessandr