ENANTIOSELECTIVE SYNTHESIS OF BIS(GAMMA-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

• Published in: Liebigs Annalen no. 2; pp. 365 - 384
• Main Authors: MENGES, M, BRUCKNER, R
• Format: Journal Article
• Language: English
• Published: DEERFIELD BEACH Wiley 01.02.1995
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; ISOTACTIC POLYMETHOXY-1-ALKENES; HMG-COA REDUCTASE; MYCOTICIN-A; POLYOL; SYN BETA-HYDROXY ETHER; GAMMA-LACTONES; POLYETHERS; REARRANGEMENTS; 2-DIRECTIONAL CHAIN SYNTHESIS; BLUE-GREEN-ALGAE; POLYENE MACROLIDE CLASS; POLYALCOHOLS; BETA-HYDROXYKETONES; 1,3-DIOL ACETONIDES; KINETIC PROTONATION; STEREOCHEMICAL ASSIGNMENT
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199519950246

The 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(gamma-butyrolactones). Two equivalents of gamma-lactone 17, readily available from L-glutamic acid, and one equivalent of the diiodoisobutene 22 furnished bis(gamma-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(gamma-lactone) cis,trans-21. On the basis of the H-1- and C-13-NMR spectral data of these and other lactones it was possible to distinguish 1,3-cis- and 1,3-trans-disubstituted gamma-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 C-13-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.