Total synthesis of enantiopure beta-D-mannosyl phosphomycoketides from Mycobacterium tuberculosis.
The first stereoselective total synthesis of a beta-d-mannosyl phosphomycoketide is reported. To introduce the stereogenic centers in the chain, three linear chiral building blocks were prepared using two different asymmetric catalytic conjugate addition protocols. Coupling of the various linear fragments was affected using a Julia-Kocienski sequence. This approach constitutes a general and convergent method for the construction of saturated oligoisoprenoid chains of any length and stereochemistry. In addition, an alternative approach for the formation of the difficult beta-mannosyl phosphate linkage was shown to be successful. Biological evalutation of the all-S compound revealed that its antigenic potency for T cells is identical to that of the natural product. This result implies that the fine structure of the lipid part has a strong influence on biological activity and that the T cell response is discriminating between different stereoisomers.
van Summeren
Ruben P
RP
Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Moody
D Branch
DB
Feringa
Ben L
BL
Minnaard
Adriaan J
AJ
D000447:Aldehydes / Q000737:chemistry; D005233:Fatty Alcohols / Q000737:chemistry; D008358:Mannose / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000378:metabolism; D010755:Organophosphates / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000447:Aldehydes; D005233:Fatty Alcohols; D010755:Organophosphates; D008358:Mannose