17 マクロリドのキラル合成 : 3.エリスロノリドAの全合成研究(その2)

抄録

An approach to the total synthesis of erythronolide A from D-glucose has been investigated. For the construction of segment i, D-glucose was converted to the olefin 6 via enone 4 in moderate yield. Then, the compound 6 was osmylated to give stereoselectively(23:1) the diol 7, which was proved to have the desired stereochemistry based on the NMR spectrum of 8 obtained from 7 by acid treatment followed by acetylation. 7 was then converted to the aldehyde 13 in good yield. However, several attempts to synthesize 15, which has all chiral centers of segment i, were found to be unsuccessful. An alternative way to prepare 15 is now under investigation. The synthesis of segment iii was completed as follows. 28 derived from 1 was converted to 30, which was then hydroborated stereoselectively(6.6:1) to give 31. The hydroxymethyl of 31 was transformed to the methyl via mesylation followed by the reduction with lithium aluminum hydride to give 32, which was converted to 34 via 33 in five steps. The cleavage between C-5 and C-6 of erythromycin A to obtain segments i and ii for the structural confirmation was successfully completed as follows. 9-Dihydroerythronolide 36, obtained from erythromycin A by the reported method was converted to 42 in 65% yield. Protection of 11,12-diol in 42, followed by the lithium aluminum hydride reduction gave 48, which was transformed easily to the tetraol 50 in three steps Finally, 50 was cleaved by lead tetraacetate to afford 51 and 52 in quantitative yield.