Total Synthesis of the Repeating Units of O-Specific Polysaccharide of Pseudomonas chlororaphis subsp. aureofaciens UCM B-306 via One-Pot Glycosylation

Abstract

Herein we report the first total syntheses of the trisaccharide-repeating units of Pseudomonas chlororaphis subsp. aureofaciens UCM B-306 via a one-pot assembly of the core trisaccharide structure. The rare-sugar-containing trisaccharide-repeating units are comprised of d-bacillosamine, 2-amino-2-deoxy-d-galacturonic acid or amide, and d-rhamnose units linked through three consecutive α-linkages. The total syntheses of two repeating units were completed starting from d-mannose via a longest-linear sequence of 27 steps in 5.8% and 4.4% overall yields, respectively.

Total Synthesis of Trisaccharide Repeating Unit of Staphylococcus aureus Type 8 (CP8) Capsular Polysaccharide

“…Further, d -fucosamine acceptor 6 was obtained by selective removal of 3-O-NAP using DDQ in 92% yield. Alternatively, a different longer route could fetch us the sole α-coupled OPMP glycoside in a d -fucosamine sugar derivative, as reported earlier …”

“…Previously, it has been observed by us that the activation of thioglycoside with PMPOH under NIS, TMSOTf/TfOH standard conditions did not progress, even after an extended reaction time. 27 Owing to this, we considered converting thioglycoside donor 7 to the corresponding trichloroacetimidate donor 8. Accordingly, treatment of 7 under NBS, THF:H 2 O (4:1) conditions generated the corresponding hemiacetal, which was then treated with trichloroacetonitrile and K 2 CO 3 , to produce the corresponding trichloroacetimidate donor 8.…”

“…Alternatively, a different longer route could fetch us the sole αcoupled OPMP glycoside in a D-fucosamine sugar derivative, as reported earlier. 27 For the synthesis of L-fucosamine donor 5, we started from known L-rhamnose triol 10 33 (Scheme 2b). A tin-mediated regioselective NAP protection at the O3 of triol 10 using Bu 2 SnO and 2-(bromomethyl)naphthalene afforded the 3-ONAP derivative 11 in 74% yield over two steps.…”

“…Such a trisaccharide can be used for making larger glycans in the quest for finding the optimal length of the antigen for vaccine development. Earlier, we have established efficient protocols involving a one-pot double displacement of 2,4-bistriflates derived from d - as well as l -sugars, which allowed a facile and expedient access to a variety of rare deoxy amino sugars, , and the glycoconjugates thereof, − including CP5 trisaccharide. Herein, we report an efficient total synthesis of CP8 trisaccharide RU 1 .…”

“…For the synthesis of d -fucosamine acceptor 6 , the one-pot double-displacement of 2,4-bistriflates approach allowed us to synthesize the well-known d -fucosamine derivative 7 from d -rhamnose thioglycoside (Scheme a). Previously, it has been observed by us that the activation of thioglycoside with PMPOH under NIS, TMSOTf/TfOH standard conditions did not progress, even after an extended reaction time . Owing to this, we considered converting thioglycoside donor 7 to the corresponding trichloroacetimidate donor 8 .…”