Library Synthesis of Polyynes against Human Colon Cancer Cells

Significance

The solid-phase synthesis of a combinatorial library of natural-product-like polyynes against human colon cancer cells was reported. For example, a triyne natural product (S)-(E)-15,16-dihydrominquartynoic acid (1) was prepared from 9-decynoic acid and a commercially available 2-Cl-trityl resin. Thus, 9-decynoic acid was loaded onto the resin to give the alkyne 2, which was converted into the corresponding bromoalkyne 3. The bromoalkyne 3 was coupled with one acetylene unit to give 4 through two-step sequence, and repeating the coupling sequence afforded 5. The cross-coupling of 5 and vinylstannane 6 with Pd(PPh₃)₄ and CuI followed by cleavage from the polymer resin afforded 1 in 23% overall yield from 2.