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 AgNO 3 /H 2 O 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 AgClO 4 to give the (4 E ,3,9‐ trans )‐ and (4 E ,3,9‐ cis )‐lactone 11 and 12 (R t ‐Bu(C 6 H 5 ) 2 Si) 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 (4 E ,3,9‐ trans )‐configuration and the (4 E ,3,9‐ cis )‐isomer 12 (RH). 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 RCOOCH 2 CH 2 Si(CH 3 ) 3 .