Efficient chemical synthesis of a dodecasaccharidyl lipomannan component of mycobacterial lipoarabinomannan.
Lipomannan (LM) is one of the domains of lipoarabinomannan (LAM) glycolipids, the latter being one of several cell surface organic molecules that fortify mycobacterial species against external attack. Some members of mycobacterial families are pathogenic, most notably Mycobacterium tuberculosis and Mycobacterium leprae, while others are nonpathogenic, and used in the clinic, such as Mycobacterium smegmatis. Additional biological significance arises from the fact that LM has been implicated in several health disorders outside of those associated with mycobacterial pathogens, notably for treatment of bladder cancer. LM is comprised of a heavily lipidated phosphoinositide dimannoside headgroup, from which a mannan array, of varied complexity, extends. The latter consists of a 1,6-alpha-linked backbone flanked at position O2, not necessarily regularly, with alpha-linked mannosides. This paper gives an example of lipomannan synthesis in which all of the sugar components, whether functioning as donors or acceptors, are obtained from n-pentenyl orthoesters, themselves in turn prepared in three easy steps from D-mannose. Assembly of the mannan array is facilitated by the exquisite regioselectivity occasioned by the use of ytterbium triflate/N-iodosuccinimide as the trigger for reaction of n-pentenyl orthoesters.
Fraser-Reid
Bert
B
Natural Products and Glycotechnology Research Institute, Inc., 595 F Weathersfield Road, Pittsboro, North Carolina 27312, USA. dglucose@aol.com
Chaudhuri
Siddhartha Ray
SR
Jayaprakash
K N
KN
Lu
Jun
J
Ramamurty
Changalvala V S
CV
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002384:Catalysis; D002855:Chromatography, Thin Layer; D004121:Dimethyl Sulfoxide; D004952:Esters; D007202:Indicators and Reagents; D008070:Lipopolysaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry; D008698:Mesylates / Q000737:chemistry; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry
D004952:Esters; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D008698:Mesylates; D009942:Organometallic Compounds; C050016:lipoarabinomannan; C064351:lipomannan; C518808:ytterbium(III) triflate; D008358:Mannose; D004121:Dimethyl Sulfoxide