Enantioselective synthesis of bis(γ‐butyrolactones). Their oxidative degradation to tetraols as a key step in stereoselective syntheses of 1,3,5,7,9‐pentaol synthons for polyhydroxylated natural products

Abstract

AbstractThe syntheses of two enantiopure skipped‐chain pentaol building blocks 51 and 56 are described. They are based on a strategy which derives 1,3,7,9‐tetraols from bis (γ‐butyrolactones). Two equivalents of γ‐lactone 17, readily available from L‐glutamic acid, and one equivalent of the diiodoisobutene 22 furnished bis(γ‐butyrolactone) trans,trans‐21 stereoselectively in a single step. The same lactone, combined in a 2:1 ratio with the dibromoisobutene derivative 18, led in four steps and with good stereocontrol to the isomeric bis(γ‐lactone) cis,trans‐21. On the basis of the 1H‐ and 13C‐NMR spectral data of these and other lactones it was possible to distinguish 1,3‐cis‐ and 1,3‐trans‐disubstituted γ‐lactones. Each of the bislactones was subject to a Criegee rearrangement of derived bis(peroxosulfonates) to give the diastereomerically pure 1,3,7,9‐tetraols 26 and 31. The configuration of these tetraols was proven by the 13C‐NMR shifts of the corresponding bis(acetonides) 27 and 32. Ozonolytic cleavage of the CC bond of 27, reduction of the obtained ketone 28 to alcohol 29, acetonide rearrangement under thermodynamic control (→ 30), and fuctionalization of the liberated hydroxy group delivered the end group‐differentiated 1,3,5,7,9‐pentaol building block 51. It represents a segment of the polyol parts of the antibiotics roxaticin (52) and mycoticin (53). The oxidative cleavage of the CC bond of bis(acetonide) 32 and chelation‐controlled reduction of the resulting ketone 33 with Zn(BH4)2 furnished after acetonide migration and functionalization of the unprotected hydroxy group the all‐syn‐configured 1,3,5,7,9‐pentaol building block 56. The latter compound should provide an entry into total syntheses of the naturally occurring poly(methyl ethers) 57 and 58.