102,060 research outputs found
Varchi, Benedetto
No full textAll'interno dell'Enciclopedia Machiavelliana ho curato la voce dedicata a Benedetto Varchi, il cui complesso rapporto con la personalità del Segretario fiorentino ho cercato di delineare di là dai tentativi dello stesso Varchi di dissimularne l'ammirazione a causa della messa all'Indice delle sue opere
Rapid microwave-assisted deprotection of N-Cbz and N-Bn derivatives
No full textCatalytic-transfer hydrogenation in ifo-propanol under microwave irradiation has been performed to rapidly deprotect N-Cbz and N-Bn derivatives. The method is particularly suitable for the synthesis of short peptides and can also be carried out on supported molecules. The rapid cleavage of chiral molecules derived from (S)-1-phenylethylamine can be very useful for asymmetric synthesis of nitrogen containing compounds. (C) 2001 Elsevier Science Ltd. All rights reserved
HPLC and circular dichroism studies on the hydrolysis of camptothecin and thiocamptothecin: the effect of sulphur on lactone stability
No full text20-(S)-camptothecin (CPT) is a naturally-occurring alkaloid isolated from the Tibetan
tree Xi Shu (Camptotheca acuminata), which displays a strong inhibitory activity
towards type I topoisomerase (topo I). [1] Severe adverse effects and the limited
stability of the lactone moiety, which plays a key role in the inhibition mechanism,
limited the clinical potential of CPT as an antitumor agent and prompted the
development of new CPT analogues with reduced toxicity and improved pharmaco-
kinetics. A thiopyridone isostere of CPT, 20-(S)-thiocamptothecin (TCPT), was recently
developed for this purpose and showed an increase in inhibitory activity in H460, HT29
and IGROV-1 cell lines, [2] probably due to the greater stability of the lactone ring.
In the present study, the kinetics of the reversible hydrolysis reactions of CPT and
TCPT (Figure 1) from the closed lactone forms (a) to the open carboxylate forms (b) were
investigated by high-performance liquid chromatography (HPLC) and electronic circular
dichroism (ECD), both in the presence and absence of human serum albumin (HSA).
HPLC analysis was performed on CPT/HSA and TCPT/HSA mixtures using UV and fluorescence detection and a restricted access media (RAM) column, which allowed the direct separation of the lactone and
carboxylate forms without any additional purification steps for the exclusion of HSA. [3]
ECD analysis was performed at fixed wavelength directly on CPT/HSA and TCPT/HSA
mixtures, after characterisation of the induced ECD of the HSA/analyte complexes.
The amount of closed lactone form in buffered solutions at equilibrium (24 h) was found
to be significantly higher for TCPT than for CPT, and the same trend was observed in
the presence of equimolar and excess quantities of HSA. Moreover, the presence of
HSA caused a shift in the hydrolysis equilibrium of CPT and TCPT towards the
carboxylate form, due to its higher affinity towards HSA with respect to the lactone
form. Nevertheless, the fraction of closed lactone form resulted higher for TCPT than
for CPT under the same experimental conditions, confirming the improved stability of
the lactone moiety. The present study provides further insights into the stabilising
effects of oxygen/sulphur replacement in the CPT pyridone ring, and represents a valid
protocol for the analysis of new CPT derivatives as potential drug candidates.
[1] R.P. Verma, C. Hansch, Chem. Rev., 2009, 109 (1), 213-235.
[2] C. Samorì, A. Guerrini, G. Varchi et al., J. Med. Chem., 2008, 51 (10), 3040-3044.
[3] M. Pistolozzi, G. Varchi, A. Degli Esposti et al., ChemMedChem, 2011, 6 (9), 1706-1714
L’Assedio di Firenze nella Storia Fiorentina di Benedetto Varchi: alcune considerazioni sulle caratteristiche della narrazione e sui tagli della committenza
No full textNella Storia Fiorentina di Benedetto Varchi l’evento storico a cui viene dato maggior rilievo è, senza dubbio, l’Assedio di Firenze:
un episodio bellico che costituisce la pietra angolare del racconto varchiano e dopo il quale, secondo le originarie intenzioni dell’autore,
doveva chiudersi l’opera. Il racconto dettagliato dei preparativi, dello svolgimento dei fatti e delle conseguenze del conflitto attraversa
ben quattro libri (IX, X, XI, XII) e Varchi si dimostra sia un profondo conoscitore degli eventi (tanto osservati direttamente, quanto
ricostruiti mediante il ricorso a varie fonti), sia un narratore efficace, che correda il minuzioso susseguirsi degli eventi con commenti
e con digressioni su vicende e personaggi. Inoltre, se si consultano i materiali originali varchiani in cui rimangono gli interventi
editoriali di chi ha curato la rassettatura finale dell’opera, ossia il granduca Cosimo de’ Medici e il suo medico personale Baccio
Baldini, si scoprirà che numerose sono le sezioni espunte nei libri dell’Assedio. L’intervento cerca dunque, dopo aver passato in
rassegna le caratteristiche della narrazione di Varchi, di analizzare le tipologie dei tagli operati dall’illustre committenza nella
campagna di revisione condotta sui libri dell’Assedio
New chiral allylaminosilanes and their use in asymmetric Sakurai reactions
No full textThe new allylaminosilanes 2a-c, derived from chiral amines, react with benzaldehyde and pivalaldehyde in the presence of SnCl4 to give homoallylic alcohols 4a-b with enantiomeric excesses of up to 30%
Synthesis of enantiopure β- and γ-amino alcohols from homochiral α- and β-aminoacylsilanes as stable synthetic equivalents of α- and β-amino aldehydes
No full textA practical route is described for the synthesis of enantiopure β- and γ-amino alcohols with two stereocenters, starting from homochiral α- (1 and 5) and β- (13 and 16) -aminoacylsilanes, and involving stereoselective addition of allylmetal compounds and subsequent stereospecific protiodesilylation of the adducts. The degree of diastereoselectivity achieved in the nucleophilic addition step depends on both the nitrogen- protecting group and the reagents used. Diastereomeric excess (de) values equal to or higher than 98% were obtained in the TiCl4-promoted allylation of the N-Pht aminoacylsilanes 1 and 13 and of the N-Ts-aminoacylsilane 5 with allyltrimethylsilane. Lower de values were obtained in the Sc(OTf)3- catalyzed anylation of 5 with tetraallyltin and in the additions of both allyltrimethylsilane and tetraallyltin to the N-Ts-β-aminoacylsilane 16. Protiodesilylation of the adducts, leading to the β- and γ-amino alcohols, was accomplished with TBAF, except in the case of the adducts obtained from 5. For these, a preliminary removal of the tosyl group was necessary, which was accomplished with simultaneous desilylation by treatment with Na in liquid ammonia
Synthesis and reactivity of achiral and of a novel planar chiral thioferrocenoylsilanes
No full textThe reactions of thioferrocenoylsilanes with organolithium reagents, dienes and reducing agents which afford α-silyl sulphides, dihydrothiopyranes and α-silyl ferrocenyl thiols, respectively, have been investigated. α-Silyl sulphides were further functionalised through carbodesilylation with aldehydes. We also report the synthesis of a new planar chiral thioferrocenoylsilane that gave good diastereomeric excess in the reaction with t-butyllithium, lithium lutidine and 2,3-dimethylbuta-1,3-diene. The 1,1′-bis-thioferrocenoylsilane, too unstable to be isolated, was trapped in situ with dienes. © 2001 Elsevier Science B.V
A convenient conversion of α-aminoacids into NH-Boc protected α-aminoketones via imidazolides
No full textImidazolides obtained from natural α-aminoacids react with a twofold excess of Grignard reagents to afford in satisfactory to good yields the corresponding NH-Boc protected α-aminoketones. Under optimized conditions the reaction with phenyl- and n-pentylmagnesium bromide required the addition of catalytic amounts of Cu(I)-salt which turned out to be unnecessary in the case of Buchi's Grignard
Extremely facile formation and high reactivity of new thioacylsilanes containing the ferrocene moiety
No full textThioacylsilanes containing the ferrocene moiety, easily prepared from the corresponding acylsilanes with Lawesson's reagent at room temperature, can be transformed into vinyl silanes, sulfur heterocycles and sulfines
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