Partially hydroxylated 2,5-disubstituted bis-tetrahydrofurans from carbohydrates

The diverse bioactivities of annonaceous acctogenins have recently attracte d increasing interest. Many of these natural products contain one or more 2 ,5-disubstituted tetrahydrofuran rings as a core unit; these are important for the bioactivity, since it is believed that these anchor the compounds t o the surface of the membrane. Therefore, the synthesis of functionalized b is-tetrahydrofurans is an important task and we have developed a synthetic pathway to all four diastereomeric, partially hydroxylated bis-tetrahydrofu rans, that is, 3,6 :7,10-dianhydro-2,8,9-tridcoxy-L-erythro-D-ido-undecitol (1), 3,6:7,10-dianhydro -2,8,9-trideoxy-D-thrco-D-ido-undecitol (2), 3,6:7 ,10-dianhydro-2,8,9- trideoxy-L-threo-D-ido-undecitol (3) and 3,6:7,10-dian hydro-2,8,9-trideoxy--erythro-D-ido-undecitol (4) starting from D-glucose. The reaction of the aldose with Meldrum's acid led to the C-glycosidic 3,6- anhydro-1,4-lactone 6, which was converted to the aldehyde building block 2 ,5-anhydro-3,4,7-tri-O-benzyl-6-deoxy-aldehydro-D-ido-heptose (11). Chain e longation of 11 with the Grignard reagent derived from 1-bromo-3-butene gav e the diastereomers 3,6-anhydro-1,4,5-tri-O-benzyl-2,8,9,10,11- pentadeoxy- L-glycero-D indo-undec-10-enitol (12) and 3,6-anhydro-1,4,5-tri-O-benzyl-2, 8,9,10,11-penta- deoxy-D-glycero-D-ido-undec-10-enitol (13). The relative t hreo configuration of the major product 12 was confirmed by X-ray structure analysis. Epoxidation and subsequent cyclization afforded the cis and tran s diastereomers 19 and 20, respectively in a 1:1 ratio. Subsequent cleavage of the protecting groups and separation of the isomers furnished the targe t compounds in good overall yields.