Boc Protection of Aminoglycosides; Hexa-NBoc Neomycin
Submitted Jul 13, 2012, published Jul 15, 2012
Neomycin (Bought as a 85:15 mixture of neomycin B and neomycin C)
The amine of interest is dissolved in a 10/10/7 solution of water, methanol and triethylamine. As the solution is stirred Boc2O(s) (1.6eq) is slowly added, with a small amount of methanol used to rinse the weigh boat/paper. The solution is then heated to 55°C for 16hr (overnight), during which time the production of t-butanol will result in a thick slurry.
Following the reaction the solution is allowed to cool to room temperature and the stir bar is removed (if possible). The slurry is evaporated to dryness on a combined high vacuum/rotary evaporator setup, using dry ice as a coolant. The resulting white solid is then left under high vacuum for a minimum of 72hr, during which time residual Boc2O will sublimate into the dry ice trap. The product may then be used without further purification, extracted if the aminoglycoside was provided as a salt, or columned to separate out isomers (ie. neomycin B from neomycin C).
1H NMR (300 MHz, MeOD) δ 5.38 – 5.12 (m, 2H), 4.92 (s, 1H), 4.21 (s, 2H), 4.10 – 3.06 (m, 20H), 2.05 – 1.88 (m, 1H), 1.71 – 1.19 (m, 55H).
Quader S, Boyd SE, Jenkins ID, & Houston TA (2007). Multisite modification of neomycin B
: combined Mitsunobu and click chemistry approach. The Journal of organic chemistry, 72 (6), 1962-79. PMID: 17298096
1H NMR Spectra for Neomycin B (NBoc Neomycin B Spectra.png)
Keywords: amines, carbamates, carbocyclic compounds, carbohydrates and sugars, heterocyclic compounds, protection