Transient Boronate Ester Mask Enables a Streamlined First Total Synthesis of Isoacteoside
Madhu Babu Tatina1,2, Duc Thinh Khong1,3, Mardi Santoso4
1School of Chemistry, Chemical Engineering, and Biotechnology, Nanyang Technological University, Singapore, Singapore.
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The first total synthesis of phenylpropanoid glycoside (PhG) isoacteoside 1 is presented. The synthesis employs a novel protection-free strategy leveraging phenylboronic acid as a transient masking agent to enable regioselective mono-rhamnosylation and caffeoylation. This method circumvents the need for traditional multi-step protection and deprotection steps and enhances overall efficiency and yield. Key steps include a one-pot, three-step glycosylation yielding β-D-glucopyranoside, regioselective rhamnosylation via in-situ boronate ester formation, selective caffeoylation at the OH-6 position, and finally one-pot deprotection to furnish isoacteoside in 26% overall yield. This work represents a significant advancement and serves as a model for preparing many PhGs with a sugar residue at OH-2 and an acyl residue at OH-6 of the 2-phenylethyl-β-D-glucoside core. This work sets a viable route for efficient PhG synthesis.
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