Zo Andriamialisoa

Synthèses Stéréosélectives des Acides 13 E et 13 Z Rétinoı̈ques via un Nouvel Intermédiaire β-Méthylènealdéhyde en C-15

Resume The methylene-de-oxo-bisubstitution reaction between dimethyl isopropylidene malonate and the C-15 β-methylenealdehyde 1 which could serve as substitute for E β-ionylideneacetaldehyde 2, produces stereoselectively the E,E olefin. Hence, new stereoselective syntheses of 13 E and 13 Z retinoic acids were described.

New preparation of an important synthon for vitamin A synthesis

Abstract The “C-18 ketone” 1, key intermediate for vitamin A synthesis, is prepared in a few steps from β-ionone 3 via β-ionylidene acetonitrile 2 (32% overall yield).

First synthesis of 9-demethyl-14-carboxyretinoic acid

Abstract A short synthesis of 9-demethyl-14-carboxyretinoic acid from β-ionone via 9-demethyl-β-ionylideneacetaldehyde is reported (48% overall yield).

A New Stereoselective Synthesis of Acitretin (= Soriatane®, Neotigason®)

A new synthesis of acitretin via a C15+C5 route is reported. The C15 unit is the key step, involving a procedure that provides the required (all-E)-C15-aldehyde with high stereoselectivity.

Stereoselective synthesis of 13Z retinoic acids via β-methylenealdehydes as synthons

Abstract A stereoselective synthesis of 13Z retinoic acids via β-methylenealdehydes is described. In methylene-de-oxo-bisubstitution reactions (Knoevenagel, Stobbe, etc.), these new synthons produce stereoselectively E olefins. Hence, a synthesis of 13Z retinoic acids is described, via a stereospecific monodecarboxylation of carboxy-14-retinoic acids.

New Synthetic Analogs of Retinoids: Synthesis of Aromatic Analogs of 9-Methylidene- and 13-Demethyl-9-methylidene-retinol, -retinal, and Ethyl 13-Demethyl-9-methylideneretinoate

Aromatic analogs of 9-methylidene and 13-demethyl-9-methylideneretinol, -retinal, and ethyl 13-demethyl-9-methylideneretinoate were synthesized via a new β-methylidene-aldehyde synthon.

Syntheses of new 9- and 13-methylene isomers of retinal

Abstract Syntheses of new 9- and 13-methylene isomers of retinal via the ‘9-methylene-C-18 ketone’ 1 or ‘C-18 ketone’ 2 are reported.

SYNTHESIS OF NEW γ- AND δ-LACTONES BY ACID CYCLIZATION OF 2,4-DIETHYLENIC-DIACIDS

We have developed an easy synthesis for new γ- and δ-lactones. Acid-catalyzed cyclization of 2,4-diethylenic-diacids yields new γ or δ-lactones, depending on the substitution pattern of the unsaturated side chain.

Synthesis of 9‐Methylene Analogs of Retinol, Retinal, Retinonitrile and Retinoic Acid

Retinoids, 9-methylene analogs of retinol, retinal, retinonitrile and retinoic acid, were synthesised from a new synthon β-methylenealdehyde.

On the photobiological properties of chimeras combining quaternary ammonium derivatives of retinoic amides and psoralen. A study with cultured human keratinocytes

The effectiveness of the combination of retinoids with 8‐methoxypsoralen (8‐MOP) and ultraviolet‐A (UV‐A) light in the treatment of some cutaneous proliferative diseases has motivated the synthesis of new “chimera‐type” molecules built from psoralen derivatives and retinoic amides and related molecules. The chimeras result from the combination of 8‐(3‐bromopropyloxy)‐psoralen with amides prepared by reacting 4‐amino‐pyridine with 13E‐ and 13Z‐retinoic acids or a “retinoid‐like” derivative with an alkene chain of only three double bonds. The synthesis of chimeras built with the 8‐(3‐bromopropyloxy)‐psoralen and the amide of cinnamic acid or its 4‐methoxy derivative has also been carried out. In contrast to 8‐MOP, all the chimeras exhibit strong molar absorptivities in the range 20 000–40 000 M−1cm−1 in the 340–390 nm UV‐A region. The “retinoid‐like”– and retinoid–psoralen chimeras are characterized by a marked dark toxicity toward proliferating NCTC 2544 keratinocytes (with a lethal dose corresponding to 50% cell survival [LD50] of 1–5 μM) as compared with that of the cinnamic acid derivative–psoralen chimeras (LD50≥ 50 μM). This toxicity leads to alteration of the mitochondrial membrane potential. At nontoxic concentrations, the chimeras demonstrate effective psoralens + UV‐A–induced photocytotoxicity. They are moderate photosensitizers of membrane lipid peroxidation. Cell apoptosis is a major photocytotoxic process as suggested by the fluorescence‐activated cell‐sorting technique using annexin–fluorescein isothiocyanate and propidium iodide as apoptotic markers.