Synthetic studies on tetrahydrofuranyl components of pamamycin-607

Abstract

For the syntheses of syn-2,5-disubstituted tetrahydrofuranyl components of pamamycin-607 1, a stereoselective iodoetherification via 5-exo process was successfully applied. Pamamycin-607 would be dissected into $C_1``-C_{11}$`` subunit 59 and $C_1-C_{18}$ subunit 60. $C_1``-C_{11}``$ subunit 59 has been synthesized starting from 79 and 121. Lactone alcohol 79 was converted into alcohol 119 over 5 steps via regioselective reductive cleavage of benzylidene acetal in 20% overall yield and alcohol 121 was derivatized into sulfone 112 over 8 steps via asymmetric crotylboration reaction in 27% overall yield. After Swern oxidation of 119, the resulting aldehyde was coupled with sulfone 112 to give 130 in 62% yield. Triethylsilyl ether of δ-hydroxy olefin 135 was prepared from β-hydroxysulfone 130 over 3 steps via Julia olefination in 33% overall yield. 135 was cyclized stereoselectively by iodoetherification to give cis-tetrahydrofuran 136 in 81% yield. $C_1``-C_{11}$`` Subunit 59 was obtained by reduction of iodide, and oxidation of hydroxyl group in sequence in 52% yield. For synthesis of $C_1-C_{18}$ subunit 60, the key intermediate 174 corresponding to $C_1-C_{13}$ moiety is now being prepared from diol 141.