40 Ecdysoneの合成 II

抄録

Synthesis of ecdysone is now in progress in our laboratory. Three key reactions for synthesis of ecdysone were developed. a) The enol form of 2,3-diketone (3) which is easily obtainable from 3-oxo steroid could be reduced by sodium borohydride into 2β,3β-diol (4) as a major product. b) Reaction of the enol acetate of 7-en-6-one (6) with monoperphthalic acid produced 14α-hydroxy-7-en-6-one (7). c) The ethynylation of aldehyde (8), followed by carboxylation gave carboxylic acid (10). This was hydrogenated and hydrolyzed to give the lactone (12), the lactone structure of which could be transformed into 22αF,25-dihydroxy compound by Grignard reaction. Acetonide of 2β,3β-dihydroxy-5α-cholestan-6-one (27) was prepared through two routes (22→23→24→25→27 and 28→29→30→31→32→27) by using the key reaction described above. The hydrolysis of (27) with 10% phosphoric acid yielded 2β,3β-dihydroxy-5α-cholestan-6-one (33a). The stereochemical problem of 2β,3β-dihydroxy-6-ones and their derivatives were examined. The treatment of (33a), (33b), (34a) or (34b) with acid or alkali gave a equilibrium mixture with ratio of 5α: 5β=3: 2. On the other hand, 5α-compound (27) is exclusively stable in acetonide series. A reasonable explanation of this difference was given. Acetonide formation reaction by phosphomolybdic acid is of interest, because reaction was found to be completed only for 10-15 minutes in spite of very weak acidity of the catalyst and any isomerization was not occurred.