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Biomedical subjects

J M Tronchet

Publications and source records attributed to J M Tronchet.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis and anti-HIV activity of thymidine analogues bearing a 4'-cyanovinyl group and some derivatives thereof.

Treatment of 3'-O-tert-butyldimethylsilyl-2',5'-dideoxy-5'-oxothymidine (4) with potassium or magnesium nitromethanide afforded in good yield the resolvable epimeric mixture of the expected blocked nitronucleosides 5 which upon dehydration led to the corresponding E-nitroenofuranosylthymidine 6. Nucleophilic attack of cyanide onto the nitrovinyl group led to a nucleoside analogue bearing a terminal 1-cyanovinyl group (7), a soft electrophilic group which, upon reaction with benzeneselenol, underwent a conjugate addition to the phenylselenonucleoside derivative 9. All these compounds, eventually de-O-silylated, were subject of in vitro biological testing, some exhibiting interesting cytotoxic or antiviral properties.

Animals↗
PubMed2000

Highly stereoselective synthesis and biological properties of nucleoside analogues bearing a spiro inserted oxirane ring.

Starting from 2',5'-di-O-TBDMS-3'-ketouridine 1 or its thymine analogue 2, both xylo (3-10) and ribo (20) epimers of a series of 3"-substituted 3'-spironucleosides have been obtained in good yields and with a total stereoselectivity. Most new compounds were moderately cytotoxic with in some cases slightly selective antiproliferative activities. None of these compounds was active against HIV, but some other antiviral activities against HSV-2, CMV, EBV, or VZV, in the micromolar range, were noted in specific cases.

Antibody-Dependent Cell Cytotoxicity↗
PubMed2000

Synthesis and antiproliferative activity of O-silylated nucleoside triazene N-oxide derivatives.

A series of modified nucleosides bearing at varied positions of the sugar moiety one 3-aryl-1-triazeno N1-oxide group and a variable number of O-TBDMS groups have been prepared and their cytotoxicities and cytostaticities measured on different cell lines. Nucleosides bearing an aryltriazeno N-oxide group and O-TBDMS groups are either devoid of cytotoxicity or possess a selective cytotoxicity. On the other hand, nucleosides bearing one triazeno group and no silyl group are devoid of cytotoxicity and silylated nucleosides without triazeno group are generally either devoid of cytotoxicity or unselectively cytotoxic. This indicates that the O-TBDMS group per se is not cytotoxic.

Animals↗
PubMed1998

Synthesis and conformational analysis of a novel type of spin labelled bicyclonucleoside based on a tetrahydrofurano[2,3-c]pyrrolidine sugar skeleton.

Bicyclonucleosides bearing a 5-deoxy-5-N-hydroxyamino-3,N5-(1,1-ethano)-beta-D-furanosyl sugar moiety (15-18) have been prepared by glycosidation of the corresponding bicyclosugars obtained via an intramolecular reverse Cope elimination. The configuration of the asymmetric carbon of the 1,1-ethano bridge is the most important factor directing the conformation of the N-hydroxypyrrolidine ring and its invertomers ratio as shown by variable temperature H NMR experiments.

Carbohydrates↗
PubMed1998

Novel spironucleosides: 1",3"-thiazolidine-2"-spiro-3'-3'-deoxyuridine derivatives.

Reaction of 2',5'-di-O-TBDMS-3'-ketouridine 1 with L-cysteine yielded in good yield a resolvable mixture of the two expected epimeric spironucleosides 2 and 3. Amidification of their carboxylic group took place readily and the ribo carboxamide 4 was oxidized to the corresponding sulfoxide 6. Despite their similarity to TSAO derivatives these compounds did not exhibit usable anti-HIV activity.

Anti-HIV Agents↗
PubMed1993

Molecular mechanical parameters (MM2 force field) for the N(sp3)-O(sp3) bond.

Based on results of MP2/6-31G* ab initio calculations an MM2 molecular mechanical parameter set has been developed for molecules containing N(sp3)-O(sp3) single bonds, existing parameters concerning the other bonds being retained. The new parameter set was tested for small organic compounds. A simple, generally applicable multilinear regression algorithm has been used and a program written to complement an existing force field (e.g. MM2) with such parameters extracted from quantum chemical computations.

Algorithms↗
PubMed1992

Structure-activity relationship between the 3D distribution of the electrophilicity of sugar derivatives and their cytotoxic and antiviral properties.

The cytotoxic activities of a series of sugar derivatives bearing electrophilic groups (1-cyanovinyl, 4-cyanochromen-2-yl and 3-nitrochromen-2-yl) have been correlated with their electrophilic properties. To this end, an electrophilic index was defined as an isovalue surface where the interaction energy with an incoming model nucleophile (H-) was equal to a predefined value. This index, calculated from extended Hückel wave functions, allows one to quantify the electrophilic character of the substrates and to describe its spatial localization within the molecular volume (at Michael acceptor sites or on other parts of the molecules). Only sugars for which Michael acceptor reactivity was predicted were retained, and they were subdivided into two groups: those showing antiviral activity against a retrovirus and those devoid of such activity. Under these conditions, good correlations between cytotoxic activity and electrophilic reactivity--positive for the first group, negative for the second--were found. In addition, the ratio electrophilicity/sum of the absolute value of the dipole plus its projection along the principal axis of inertia, Z, of the molecule allows one to predict to which of these groups a sugar derivative belongs.

Antineoplastic Agents↗
PubMed1992

Spin-labelled sulfur containing neoglycolipids.

A neoglycolipid of structure beta-D-Glcp-S-(CH2)3N(OH)(CH2)4-O-cholest-5-en-3 beta-yl has been prepared in fair overall yield by reduction of the nitrone obtained by condensation of beta-D-Glcp-S-(CH2)3NHOH and OCH-(CH2)3-O-cholest-5-en-3 beta-yl. This synthetic procedure is very flexible, allowing a large range of lengths for the spacer arm, different positions for the NOH group along the spacer arm chain and the replacement of the sulfur by other bio-isosteric groups. The new neoglycolipid spontaneously oxidized to the corresponding nitroxide free radical whose EPR spectrum gave information on its conformational equilibrium which was further studied by molecular mechanics.

Glycolipids↗
PubMed1991

[Stable copper complexes derived from nitrogen sugars].

This paper describes the synthesis of six new well-defined, stable cupric complexes of the general formula Cu(Ligand)2 in which the organic ligand is a nitrogen-bearing sugar derivative. Some of these compounds showed a border-line cytotoxic activity.

Antifungal Agents↗
PubMed1990

[Synthesis and anticonvulsant properties of sugar triazene N-oxides].

In this paper we describe a high-yielding method leading to a novel family of sugars: the sugar triazene N-oxides. The anticonvulsant effect of one of these compounds was tested. It showed a promising activity indicating the potential therapeutic usefulness of this class of carbohydrate derivatives.

Animals↗
PubMed1989

Structures of 5-bromo-6-ethoxy-5,6-dihydrouridine and -thymidine derivatives, a class of potential antitumoral and antiviral N-nucleosides.

(I): (+)-(5R,6R)-5-Bromo-6-ethoxy-5,6-dihydro-2',3'-isopropylidene-beta-D- ribofuranosyl-uracil, C14H21BrN2O7, m.p. 408.7-409.6 K, [alpha]D23 degrees C = +31.1 degrees (c = 1.2% in MeOH), Mr = 409.2, monoclinic, P2(1), a = 9.218 (2), b = 9.6619(11) c = 10.4938 (14) A, beta = 99.305 (8) degrees, V = 922.4 (2) A3, Z = 2, Dx = 1.47 Mgm-3, lambda (Mo K alpha) = 0.71069 A, mu = 2.24 mm-1, F(000) = 420, room temperature, R (= wR) = 0.046 for 2595 observed reflections [(Fo)] greater than 4 sigma (Fo) and (Fo) greater than 8.0]. (II): (+)-(5R,6R)-5-Bromo-2'-deoxy-6-ethoxy-5,6-dihydro-beta-D-ribofuranosyl- thymine, C12H19BrN2O6, m.p. 376.1-376.5 K, [alpha]D 23 degrees C = + 58.8 degrees (c = 1.02% in MeOH), Mr = 367.2, monoclinic, clinic, P21, a = 6.0428 (9), b = 8.5270 (15), c = 14.589 (2) A, beta = 96.80 (1) degrees, V = 746.4 (1) A3, Z = 2, Dx = 1.63 Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.75 mm-1, F(000) = 376, room temperature, R = 0.053 (wR = 0.040) for 1579 observed reflections [[F0[ less than 4 sigma(Fo)]. Both furanose rings adopt an envelope conformation with C(4')-exo and C(1')-exo for (I) and (II) respectively. The orientation of the dihydropyrimidine base relative to the sugar ring shows an unusual syn conformation [chi CN = 62.5 (6) degrees] for (I) whereas the glycosyl linkage of compound (II) shows an anti conformation [chi CN = -134.0 (8) degrees]. In both compounds the pyrimidine ring displays a half-chair form. The conformation of the hydroxymethyl group at C(4') is gauche-gauche for (I) [phi OO = -68.2 (7) degrees, phi OC = 50.1 (8) degrees] and trans-gauche for (II) [phi OO = 180 (1) degrees, phi OC = -61 (1) degrees]. The absolute configuration of (I) was confirmed by least-squares refinement of x [x = 0.008 (16)] [Bernardinelli & Flack (1985). Acta Cryst. A41, 500-511] and that of compound (II) deduced from the starting material. An intramolecular hydrogen bond occurs between the hydroxymethyl and the pyrimidine of (I). In both structures, the molecular packing is fixed by a network of hydrogen bonds.

Antineoplastic Agents↗
PubMed1976

Electron impact mass spectrometry of some ketosugar derivatives.

The electron impact fragmentation of 1,2-O-isopropylidene-alpha-D-glycero-tetros-3-ulofuranose has been studied with the help of deuterium and 18O labelling. The effect of substituting a hydrogen atom of C-4 for a CH3 radical and that of replacing the carbonyl function with a cyanomethylenic substituent is also reported.

Electrons↗