Retrosynthetic Analysis for Lipid

The diversity of structural elements present in lipid I mandated a synthetic plan that would efficiently manage variables such as structural 

Our first disconnection revealed glycosyl monophosphate 7 and undecaprenyl monophosphate 8.11 This disconnection was chosen because previous work, directed toward the synthesis of the Park Nucleotide 3, had shown it possible to introduce an anomeric phosphate with anomeric selectivity in favor of the desired a-anomer. A second reason for choosing this disconnection was that undecaprenyl monophosphate was available for purchase from a commercial source. Thus, if we could identify a mild method for joining these two fragments, only a global deprotection step would be required to arrive at lipid I. 

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Our retrosynthetic analysis for lipid I is presented below [Scheme 2], Our protected version of lipid I employed acetate protective groups for the carbohydrate hydroxyls, methyl esters for each of the carboxyl groups in the pentapeptide side chain, and trifluoroacetate for the terminal amino group of the lysine residue. These base-cleavable protective groups could be removed in a single operation in the final step of our synthesis and would not subject the sensitive diphosphate linkage to acidic reagents or reaction conditions. 

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