New Approach Towards Cytotoxic Furyl Macrolactones by Ring Closing Metathesis.

Abstract

Metathesis. -Ring closing metathesis to title compounds (IV) is achieved by using Grubbs' catalyst. The resulting E/Z mixtures are separable by GLC. The lactones (IV) and the ring opening product (VI) show weak cytotoxic activitiy against HL-60 cells.

Synthesis by Ring Closing Metathesis and Cytotoxic Evaluation of Novel Thienylmacrolactones

“…To our great surprise, the secondary thienyl carbinol 2 showed very interesting cytotoxic activity (IC 50 = 6 μM). This reminds us of an accidental observation in previous work [ 12 ] where a side-product containing a furyl carbinol showed comparable cytotoxicity.…”

“…When using Grubbs II catalyst, the reaction proceeded faster than with Grubbs I catalyst (6 h vs. 24 h), for comparable observations see ref. [ 12 , 16 , 17 ].…”

“…The target compounds were to be prepared using the ring-closing metathesis methodology we worked out earlier for various furyl macrolactones [12, 13]. …”

“…This prompted us to investigate a new type of 16-membered lactones bearing a sulphur-containing hetarene, namely a thiophene ring [ 11 ], next to the lactone oxygen in analogy to new synthetic epothilones. The target compounds were to be prepared using the ring-closing metathesis methodology we worked out earlier for various furyl macrolactones [ 12 , 13 ].…”