Synthesis of salinomycin

Abstract

Salinomycin, a commercially significant coccidiostat isolated from Streptomyces albus, has been synthesised from three principal fragments. Key steps include (a) the use of η³-allylmolybdenum cationic complexes 21a,b for the stereoselective construction of two contiguous stereogenic centres in fragment 5a; (b) the electrophilic cyclisation of 2-(prop-2-ynyl)-2-hydroxyoxanes to give molybdenum and chromium carbene complexes which are precursors to the furan fragment 7; (c) the diastereoselective oxidation of a 1,5-diene with potassium permanganate to generate four stereogenic centres in a single step leading to fragment 8; (d) the oxidative rearrangement of acylfuran 89 en route to the 1,6,8-trioxadispiro[4.1.5.3]pentadec-13-ene dispiroacetal core; and finally (e) the use of an allenol ether as an acyl anion equivalent together with the stereoselective hydrolysis of allenol ether intermediate 112 in an alternative synthesis of the dispiroacetal core.