Synthetic studies on statine

Abstract

For total synthesis of statine 1, the formation of bicyclic lactam 27 was attempted as a key intermediate. Mesylate dihydrofuran 39 was prepared from D-glyceraldehyde via incomplete iodoetherification with rather low chemical yields. Sharpless epoxidation of dienol 43 to obtain 45 was not accomplished. Acetonide 50 was prepared in low chemical yields by wittig olefination of phosphonium salt 47 and aldehyde 49 which was derived from triol acetonide 48. Finally, dihydrofuranylamide 70, a promising precursor to 27, was developed from lactone 66. Reduction of 66 followed by wittig olefination gave protected alcohol 67 in high chemical yield. Alcohol 67 was readily converted to amide 70 via mesylation, iodoetherification, elimination, conversion to nitrile and hydrolysis. For the synthesis of 27, cyclization of amides 70, 73 and 74 was attempted under various reaction conditions. But not lactam 27 but lactone 75 was obtained. Conversion of amides 70, 73 and 74, and nitrile 69 into imidates or amidine was not succeeded.