Synthese von (±)‐Diplodialid B und A

Synthesis of (±)‐Diplodialide B and A Two steroid hydroxylase inhibitors, diplodialide B (1) and A (2) have been synthesized in the following way: The lithium enolate 5 of S‐t‐butyl thioacetate (4) was added to (E)‐7‐(2′‐tetrahydropyranoxy)‐2‐octen‐1‐al (8) and the newly formed 3‐hydroxy group in the product 9 was protected as t‐butyl‐diphenyl silyl ether followed by selective hydrolysis of the tetrahydropyranyl ether to give 10. Treatment with AgNO3/H2O cleaved the S‐t‐butyl ester group in 10 to give the corresponding hydroxy carboxylic acid which was converted into the S‐2‐pyridyl thioester by treatment with di(2‐pyridyl)disulfide and triphenyl phosphine and cyclized with AgClO4 to give the (4E,3,9‐trans)‐ and (4E,3,9‐cis)‐lactone 11 and 12 (Rt‐Bu(C6H5)2Si) in 67% yield. Chromatographic separation of 11 and 12 and cleavage of the t‐butyl‐diphenyl silyl ether with tetrabutyl ammonium fluoride yielded (±)‐diplodialide B (1) with (4E,3,9‐trans)‐configuration and the (4E,3,9‐cis)‐isomer 12 (RH). Both isomers could be oxidized to diplodialide A (2) with manganese dioxide. The synthesis described above has also been carried out via the intermediates 10, 11 and 12 with RCOOCH2CH2Si(CH3)3.