Total synthesis, isolation, surfactant properties, and biological evaluation of ananatosides and related macrodilactone-containing rhamnolipids

Abstract

We show that macrolactonization of gluco- and rhamnolipids dramatically interfere with their surfactant properties and biological activity.

Total Synthesis of a Chimeric Glycolipid Bearing the Partially Acetylated Backbone of Sponge-Derived Agminoside E

“…These oligosaccharides would be obtained from five conveniently functionalized STol or trichloroacetimidate (TCA) 26 building blocks (4a, 5a, 6, 7a, and 8) and benzyl ester 9. 27 The presence of a (2azidomethyl)benzoyl (AZMB) 28 group at the C2 position of residues 4a, 6, and 7a would ensure the formation of βglucosidic bonds via NGP. The AZMB group would be orthogonally cleaved through hydrogenolysis or Staudinger reduction, hence preserving the integrity of the acetylation pattern.…”

“…The AZMB group would be orthogonally cleaved through hydrogenolysis or Staudinger reduction, hence preserving the integrity of the acetylation pattern. 27 The AZMB group would be favored over a chloroacetyl group because of the basic conditions needed to remove the latter that could trigger acetyl migration. In addition, the presence of a levulinoyl (Lev) 29 ester in building block 7a would allow the selective unmasking of the C4 hydroxyl position prior to the formation of the final β-(1 → 4)glucosidic bond between residues B and A.…”

“…As far as we are aware, although the NIS/Yb(OTf) 3 promotion system was successfully imple- mented by Fraser-Reid and co-workers for the activation of npentenyl orthoesters, 52,53 it has only been sporadically reported for thioglycosides. 27,52,54,55 Having achieved the synthesis of the "western" disaccharide 31, we then focused our attention on the synthesis of the "eastern" glycolipid 3, also involving the formation of a β-(1 → 4) linkage. As a first step, we sought to study the glycosylation behavior of our newly developed STol donor 7a using benzyl 12-hydroxydodecanoate (32) as a model glycosyl acceptor (Table 3).…”

“…We were pleased to find that applying our optimized NIS/ Yb(OTf) 3 conditions for the coupling between glycosyl donor 7a and benzyl (R)-3-hydroxydecanoate ( 9) 27 furnished glycolipid 35 in 70% yield without a noticeable formation of the orthoester (Scheme 3A). The AZMB group was then removed via Staudinger reduction giving C2 alcohol 36 (87%) ready for the formation of the (1 → 2)-branched linkage.…”

“…As retrosynthetically depicted in Figure , chimeric glycolipid 1 would come from a [3 + 2] glycosylation between trisaccharide 2 , in the form of a thiotolyl (STol) glycoside, , and branched glucolipid 3 . These oligosaccharides would be obtained from five conveniently functionalized STol or trichloroacetimidate (TCA) building blocks ( 4a , 5a , 6 , 7a , and 8 ) and benzyl ester 9 . The presence of a (2-azidomethyl)­benzoyl (AZMB) group at the C2 position of residues 4a , 6 , and 7a would ensure the formation of β-glucosidic bonds via NGP.…”