Efficient tin-mediated synthesis of lysophospholipid conjugates of a TLR7/8-active imidazoquinoline.

The chemical synthesis of lysophospholipids often involves multiple synthetic and chromatographic steps due to the incorporation of the fatty acyl group onto the glycerol scaffold early in the synthesis. We report herein a new protocol for the lysophosphatidylation of alcohols and its application to the synthesis of lysophospholipid conjugates of TLR7/8-active imidazoquinoline 3. This new procedure, which is based on the tin-mediated regioselective acylation of late-stage phosphoglycerol intermediate 17, overcomes many of the drawbacks of conventional lysophosphatidylation methods and allows introduction of different fatty acyl groups in the penultimate step.