Optimization of a Chemical Synthesis for Single-Chain Rhamnolipids

This work reports efforts to improve the efficiency and green metrics associated with the chemical synthesis of single-tailed monorhamnolipids. Scaling of synthetic schemes for monorhamnolipids recently reported from this laboratory has been challenging, as large-scale production typically requires high-pressure equipment and an inert atmosphere due to the pyrophoric nature of a palladium/carbon (Pd/C) catalyst used for a key deprotection step. Furthermore, using Reformatsky condensation in conjunction with a methyl ester carboxylic acid protecting group, a safer, simpler, and "greener"synthetic pathway to 3-hydroxyalkanoic acid lipid tails is achieved. The two diastereomers of the resulting single-tail rhamnolipids from both 3-hydroxydecanoic acid and 3-hydroxytetradecanoic acid lipid chains are separated and independently characterized. Surface tensiometry was performed on these materials at pH 4 (acid neutral state) and 8 (acid anionic state). All rhamnolipids exhibit minimum surface tension values of 30-36 mN/m. Large differences in critical micelle concentration (CMC) values are observed between diastereomers for α-rhamnose 3-hydroxydecanoic acid at pH 4, with α-rhamnose (R)-3-hydroxydecanoic acid having a CMC of -380 μM compared to 1.7 mM for α-rhamnose (S)-3-hydroxydecanoic acid. For α-rhamnose 3-hydroxydecanoic acid diastereomers at pH 8, the CMC values differ slightly for the two diastereomers, with α-rhamnose (R)-3-hydroxydecanoic acid at 13 mM and α-rhamnose (R)-3-hydroxydecanoic acid at 21 mM. Similarly, CMC values of the two α-rhamnose 3-hydroxytetradecanoic acid diastereomers at pH 4 are similar at -100 μM but exhibit large differences at pH 8, with the racemic and α-rhamnose (R)-3-hydroxytetradecanoic acid with a CMC value of -500 μM and the α-rhamnose (S)-3-hydroxytetradecanoic acid exhibiting a CMC value of 1.8 mM.