ALCLASS · Application of Lithiated Carbamates to the Asymmetric Synthesis of Sulfolipid-I
FP7 — People (Marie Curie Actions)
- Duration
- 2012-07-01 → 2014-06-30
- EU contribution
- €209,033
- Participants
- 1
- Scheme
- MC-IEF
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Results in brief
Application of Lithiated Carbamates to the Asymmetric Synthesis of Sulfolipid-I
In planning organic syntheses, disconnections are most often made adjacent to functional groups, which assist in C–C bond formation. For molecules devoid of obvious functional groups this approach presents a problem, and so functionalities must be installed temporarily and then removed. Here we present a traceless strategy for organic synthesis that uses a boronic ester as such a group in a one-pot lithiation–borylation–protodeboronation sequence. To realize this strategy, we developed a methodology for the protodeboronation of alkyl pinacol boronic esters that involves the formation of a boronate complex with a nucleophile followed by oxidation with Mn(OAc)3 in the presence of the hydrogen-atom donor 4-tert-butylcatechol. Iterative lithiation–borylation–protodeboronation allows the coupling of smaller fragments to build-up long alkyl chains. We employed this strategy in the synthesis of hydroxyphthioceranic acid, a key component of the cell-wall lipid of the virulent Mycobacterium tuberculosis, in just 14 steps (longest linear sequence) with full stereo control. The synthesis of primary and secondary pinacol boronic esters via lithiation–borylation of carbamates and benzoates with pinacol borane is described. This new protocol enables the highly selective synthesis of enantioenriched and geometrically defined boronic esters that cannot otherwise be accessed by alternative methodologies.
Data: CORDIS, © European Union
Project objective
Mycobacterium tuberculosis, the causative agent of human tuberculosis, is unique among bacterial pathogens. Sulfolipid-I (SL-I) is the major constituent metabolite of thick cell wall present in Mycobacterium Tuberculosis (M-TB). SL-I comprises of a disaccharide and four chiral hydrophobic lipid substituents, the overall structure of which is responsible for the resistance of M. Tuberculosis to antibiotics. While SL-I has been shown to elicit specific responses from immune cells, the mechanistic basis of these effects, biosynthesis and biological activities are unknown. Although a number of studies have been reported on the synthesis of disaccharide core and hydrophobic lipids of SL-I, major challenges reside in the synthesis of chiral hydrophobic lipids, which comprise multiple stereocenters. It is aimed to synthesis the enantiopure sulfolipid-I in a short synthesis by utilizing the recent methodology developed by the Aggarwal group involving the reactions of chiral lithiated carbamates with boronic esters. This new strategy is a potentially powerful tool for the iterative asymmetric synthesis of complex molecules in short order.""
Original text from CORDIS.
Participants
- UNIVERSITY OF BRISTOL · BRISTOLCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union