Exploiting the vicinal disubstituent effect on the diastereoselective synthesis of γ and δ lactones

Abstract

Trifluoroacetic acid catalysed lactonization of vicinal disubstituted γ-hydroxyesters was investigated in different solvents.

A chiral trimethyl lock based on the vicinal disubstituent effect: prolonged release of camptothecin into cancer cells

“…Recently, we studied the acid-catalysed cyclization of a series of alkyl substituted γ- and δ-hydroxy esters and we found that the cyclization rate depends on the relative stereochemistry of the vic -disubstituted precursors ( vic -disubstituent effect), regardless of the catalyst, the leaving group and the solvent used. 8 More precisely, in the case of γ-hydroxy esters, the syn dimethyl substituted diastereoisomer showed a kinetic behaviour quite similar to its gem -dimethyl constitutional isomer, whereas, the anti diastereoisomer ring-closed to the trans lactone almost 20 times faster; analogously, even for the δ-hydroxy esters a vic -disubstituent effect was observed (Fig. 1C).…”

Fluoride‐Triggered Self‐Degradation of Poly(2,4‐disubstitued 4‐hydroxybutyric acid) Derivatives

“…In fact, the cyclization reaction of substituted 4‐aminobutyric acids and 4‐hydroxybutyic acids has been investigated, and increase of cyclization rate by substitution has been confirmed. [ 37–43 ] To this end, we propose to introduce a methyl group into the α ‐position of the ester bond of poly(4‐hydroxybutyric acid) derivative (Scheme 1). Furthermore, to realize the trigger‐induced self‐immolative property, we anchored a silyl ether group to the polymer chain end.…”