Monensin synthesis

Yield:-

Reaction Conditions:

with sulfuric acid in dichloromethane;water; pH=1.5

Steps:

4.2. Preparation of monensin A amide with AB15C5 amine
Monensin A sodium salt (MON-Na) was dissolved in dichloromethane (CH₂Cl₂) and stirred vigorously with a layer of aqueous sulfuric acid (H₂SO₄; pH=1.5). The organic layer containing MONA was washed with distilled water, and dichloromethane was then evaporated under reduced pressure to dryness. A solution of MONA (1000 mg, 1.49 mmol), 1,3-dicyclohexylcarbodiimide (DCC-515 mg, 2.50 mmol) and 4-aminobenzo-15-crown-5 (AB15C5-1133 mg, 4.00 mmol) all dissolved in dichloromethane and 1-hydroxybenzotriazole (HOBt-330 mg, 2.44 mmol) dissolved in tetrahydrofuran was mixed together and stirred at a temperature between 0 and -10 °C for 24 h. After this time the reaction mixture was stirred at room temperature for the next 24 h, diluted with H₂O and extracted with CH₂Cl₂. The organic phase was evaporated under reduced pressure to dryness. The residue was suspended in hexane and filtered off to remove 1,3-dicyclohexylurea (DCU) as a by-product. The filtrate was evaporated under reduced pressure and purified by chromatography on silica gel (Fluka type 60) to give M-AM3 (988 mg, 71% yield) as an amorphous, brown solid.Elemental analysis for M-AM3 (C₅₀H₈₁NO₁₅): Calculated: C 64.15%, H 8.72%, N 1.50%. Found: C 64.05%, H 8.78%, N 1.61%.Furthermore, M-AM3 and its 1:1 and 1:2 complexes with sodium perchlorate were fully characterised by ESIMS, ¹H, ¹³C NMR and FTIR spectroscopy.

References:

Łowicki, Daniel;Huczyński, Adam;Stefańska, Joanna;Brzezinski, Bogumil [Tetrahedron,2011,vol. 67,# 7,p. 1468 - 1478] Location in patent:experimental part

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