Divergent total synthesis of crassalactones B and C and evaluation of their antiproliferative activity

A divergent total synthesis of cytotoxic natural products (+)-crassalactones B (2) and C (3) has been achieved by utilizing diacetone D-glucose (4) as a chiral precursor. The key steps of the synthesis of both targets 2 and 3 were a stereo-selective addition of phenyl magnesium bromide to a dialdose derivative, a regioselective introduction of the cinnamic acid residue, and a stereospecific furano-lactone ring formation by cyclocondensation of a suitable hemiacetal derivative with Meldrum's acid. No protection is necessary for the synthesis of the (+)-crassalactone C (3), except the diacetonide function that is already present in the commercially available starting material 4. Preparation of (+)-crassalactone B (2) from the same starting material, requires the use of a single silyl ether protecting group throughout the synthesis. The synthesized natural products were evaluated for their in vitro antiproliferative activity against PC3, HT29 and A549 human tumour cell lines. (C) 2015 Elsevier Ltd. All rights reserved.