Alain Doutheau

Synthese d'amino-alcools alleniques.

Abstract The entitled alcohols are obtained by reaction of cuprous reagents with α-acetylenic epoxides bearing a phtalimido group in α position, followed by hydrazinolysis. They show an inhibitory effect on the growth of certain transformed cells in tissue culture.

Attaque nucleophile du carbone central de l'enchainement cumule lors de la cyclisation de diols ω,ω′-alleniques

Abstract The cyclisation of allenic diols 3 and 4 in the presence of mercuric chloride or silver nitrate leads exclusively or predominantly to bicyclic acetals 6 and 8 resulting from an initial nucleophilic attack on the central allenic carbon. This regioselectivity depends on the presence of a terminal methylene in the unsaturation since diol 5 leads to the dihydropyrane 12 coming from the nucleophilic attack on the terminal allenic carbon.

Preparation d'α-alcenyl-2 tetrahydropyrannes par cyclisation d'alcohols δ-alleniques.

Resume Four δ-allenic alcohols, prepared in several steps from dihydropyrane or from δ-valerolactone were cyclized with good yields to 2-alkenyl tetrahydropyranes using silver nitrate r mercurin trifluoroacetate.

Malondialdehyde production from spermine by homogenates of normal and transformed cells

The oxidation of spermine in vitro by a mixture of polyamine oxidase and diamine oxidase from pig kidney gives rise to malondialdehyde via 3-aminopropanol as the intermediate. Conversely, with spermidine, under similar experimental conditions, no evidence could be obtained for malondialdehyde formation within the limits of sensitivity of the assay (2.0 nmol). The activities of both these enzymes show about a 2-fold increase in normal rat kidney cells (LA31 NRK) transformed by the temperature sensitive mutant of Rous sarcoma virus (LA31) and incubated at the non permissive temperature (39 degrees C) compared to the activities in LA31 NRK at the permissive temperature (33 degrees C). These same enzymatic activities show no temperature dependent changes in normal rat kidney cells (NRK) or in these same cells infected by the wild type virus (NRK B77). In extracts derived from Friend erythroleukemic cells induced to differentiate by dimethyl sulfoxide or hexamethylene bis acetamide, spermine oxidation takes place more efficiently than in non induced cells. A rise in diamine oxidase activity is seen in LA31 NRK (39 degrees C) 12 h after the temperature shift, whereas morphological manifestations of normalcy are seen only at 48 h. The Km of diamine oxidase is 10(-6) M for putrescine and 10(-3) M for 3-aminopropanol. A possible mechanism involving the well documented acetylation of putrescine [23,26] is proposed for diverting intracellular putrescine away from cytosolic diamine oxidase and towards intramitochondrial monoamine oxidase.

Synthese et cyclisation oxydante de triene-2,3,5 ols-1 en hydroxyalkyl-5 cyclopentene-2 ones-1

Resume Cinq tnene-2,3,5 ols-1 1 ont ete synthetises en faisant appel a trois methodes. Leur reaction avec le peroxyde de t-butyle en presence de quantites catalytiques dacetylacetonate de vanadyle conduit tres majoritairement aux cyclopentenones 2 . La sequence constitue une nouvelle voie dacces a la methylenomycine B 3 .

Oxydation d'alcools ω-vinylalléniques par l'hydroperoxyde de tertiobutyle

Resume Loxydation des alcools α-vinylalleniques 3 par lhydroperoxyde de tertiobutyle en presence de quantites catalytiques dacetylacetonate de vanadyle conduit, soit aux epoxydes 6, soit majoritairement aux cyclopentenones 5, suivant la nature secondaire ou tertiaire de la fonction alcool. Dans les memes conditions, les alcools β-vinylalleniques 4 conduisent aux seules cyclopentenones 7.

Heterocyclisation de diols βγ′-alleniques.

Abstract The silver nitrate assisted cyclization of the entitled diols 3 leads, depending on the substitution of the allenic linkage, specifically to dihydropyranes 4 , when R is alkyl or to an equimolecular mixture of 4 and its tetrahydrofuranyl isomer 5 when R is hydrogen.

γ-amino α-acetylenic epoxides: Preparation and biological activity due to an aldehyde reductase inhibition

Abstract The preparation of several of the entitled epoxides 3 is described in two steps starting from 2-methyl 2-amino but 3-yne, the first one being the reaction of the lithium acetylide with a α-chloroaldehyde or ketone. In certain cases, this reaction Is highly diastereoselectlve giving 96% of the R ∗ S ∗ diastereoisomer. One of these epoxides ( 3a ) inhibits very selectively the growth of transformed cells. This activity is due to the inhibition of aldehyde reductase, an enzyme involved in the intracellular transformation of malonaldehyde derived from polyamines into 1,3-propanediol.

New preparation of α-allenic ketones

Abstract The ketal aldehyde 2 is the starting material of a two-step synthesis of α-allenic ketones 1 γ-substituted with a functionalized chain.

Synthesis of α-Functionalized Allenes

Abstract It is known, since the work of Landor et al, that α-allenic alcohols can be specifically obtained by treating the monotetrahydropyranyl ether of a butyn-1,4-diol with lithium aluminium hydride (1). In this reaction, which can be also realized with another leaving group (halogen, ammonium) (2), the allenic linkage is formed by an SN 2′ process where the nucleophilic hydride is transferred from the initially formed alcoholate (scheme 1).