The structure of the capsular polysaccharide (CPS) of serotype Ia group B Streptococcus (GBS) has been characterized for years, but its repeating unit, which is a challenging pentasaccharide with a branch and a difficult α-sialic acid linkage, has not been synthesized yet. In this report, an effective synthesis was developed for the serotype Ia GBS CPS repeating unit, which had a reactive functionality linked to its main chain reducing end to enable further elaboration, such as coupling with carrier proteins. The target molecule was accomplished by a convergent [2+3] glycosylation strategy employing a sialo-disaccharide as donor and a branched trisaccharide as acceptor. The strategy was designed to suit the synthesis of oligomers of the repeating unit.
An enantiocontrolled synthesis pathway has been developed to provide formation of tricyclic amine 7, representing the ABC ring system of the complex alkaloid daphnicyclidin A (1). Our efforts describe preparation of the Z-hexahydro-(1H)-azocine 29 and cyclization to construct the novel 4-azabicyclo[5.3.2]dodecane 31. Transannular reductive amination following the deprotection of 31 gave the desired tertiary amine 7.
An efficient approach to the parallel synthesis of benzimidazoles
from anilines is described. Library approaches to vary the N1 and
C2 vectors of benzimidazoles are well established; however, C4–C7
variation has traditionally relied on 1,2-dianiline building blocks,
providing limited chemical space coverage. We have developed an amidine
formation/oxidative cyclization sequence that enables anilines as
a diversity set for benzimidazole C4–C7 SAR generation in parallel
format. The amidine annulation was achieved using PIDA or Cu-mediated
oxidation to access both N–H and N–alkyl benzimidazoles.
This library protocol has now been utilized for analog production
in four medicinal chemistry projects. Additionally, the synthesis
of aza-benzimidazoles from aminopyridines was achieved via an analogous
sequence.
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