Synthesis of a polyphosphorylated GPI-anchor core structure

• Using a linear assembly approach a highly differentially protected derivative of the common GPI-anchor core structure (alpha-D-Man-(1-->6)-alpha-D-Man-(1-->2)-alpha-D-Man-(1-->4)-alpha-D-GlcNH(2)-(1-->6)-D-myo-inositol) has been synthesized. All mannose donors were prepared from a common thioglycoside precursor (1), and coupled to GlcN(3)-myo-inositol acceptor 5 in a linear five-step glycosylation-deprotection sequence in 49% overall yield, to give the key intermediate 10, with orthogonal temporary protecting groups at the 6", 2", 6', and 2 positions of the trimannoside motif and at the 1 and 2 positions of the inositol part. Consecutive removal of the temporary protecting groups in the trimannoside moiety followed by phosphorylation, gave a tetraphosphosphate derivative in 60% overall yield. Removal of a camphor acetal afforded a 1,2-inositol diol, which was converted to a 1,2-cyclic phosphate using commercial methyl dichlorophosphate (-->17, 95%). One-step deprotection using sodium in liquid ammonia afforded the target polyphosphorylated core structure 18 (60%), which will be tested for metabolic insulin action.

Ämnesord

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

Nyckelord

glycophosphatidylinositols

linear synthesis

glycosylations

mositolphosphoglycans

IPG

TECHNOLOGY

TEKNIKVETENSKAP

Publikations- och innehållstyp

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