Undecaprenyl monophosphate

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. 

Phosphoromorpholidate intermediates, initially developed by Khorana and Moffatt,19 have been widely used for the construction of nucleoside diphosphates. The construction of the diphosphate linkage typically involves exposure of a carbohydrate-derived phosphate nucleophile to phosphoromorpholidate electrophile in pyridine solvent. This protocol was attractive from the point of view that it can be executed on completely deprotected precursors. This method suffers, however, from the lengthy reaction times required for reasonable conversion, although a tetrazole modification, introduced by Wong, had been shown to shorten reaction times considerably. The major drawback of this method, for our own purposes, is that it would require construction of either a carbohydrate-derived phosphoromorpholidate or the preparation of a phosphoromorpholidate intermediate deriving from our rather expensive undecaprenyl monophosphate precursor. 

Similar concerns regarding the stability of our activated lipid intermediate led us to reject a method that involves the in situ preparation of lipid-derived phosphoric anhydrides.22 The common theme for each of the methods illustrated above is that each involves activation of the lipid intermediate for the diphosphate coupling reaction. Given the expense of the undecaprenyl monophosphate precursor, we sought a method that would entail activation of the carbohydrate fragment for capture by an undecaprenyl monophosphate nucleophile. This, in principle, would also allow the opportunity for the coupling reaction to take place under basic reaction conditions and enable us to preserve the chemical integrity of our expensive lipid precursor. 

Undecaprenyl monophosphate bis-ammonium salt may be purchased from Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul. Pawinskiego 5A, 02-106 Warszawa, Poland. 

The complex is transferred to the outside surface of the cell membrane, then released, leaving un-decaprenyl pyrophosphate, a) The monophosphate of undecaprenol is regenerated by the action of a specific phosphatase, and the energy of this hydrolysis appears to be utilized in moving the undecaprenyl monophosphate back to the inside surface of the membrane. The antibiotic activity of Bacitracin (see) is due to its inhibition of this pyrophosphate cleavage, b) Complexes combine into linear polymers. 

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