Synthesis of Psoralidin derivatives and their anticancer activity: First synthesis of Lespeflorin I1

Abstract

Synthetic scheme for the preparation of a number of different derivatives of anticancer natural product Psoralidin is described. A convergent synthetic approach is followed using simple starting materials like substituted phenyl acetic esters and benzoic acids. The developed synthetic route leads us to complete the first synthesis of an analogous natural product Lespeflorin I₁, a mild melanin synthesis inhibitor. Preliminary bioactivity studies of the synthesized compounds are carried out against two commonly used prostate cancer cell lines. Results show that the bioactivity of the compounds can be manipulated by the simple modification of the functional groups.

Fig. 1

Psoralidin and structurally similar bioactive natural products.

Scheme 1

Synthesis of derivatives with substitution at C-2.

Scheme 2

Synthesis of Psoralidin analogs 29–32.

Scheme 3

Synthesis of allylated coumestanes 39–41

Scheme 4

Synthesis of triacetates and their deprotection

Scheme 5

Synthesis of Lespeflorine I₁ (2) and analogs