Paper
Organic & Biomolecular Chemistry
ate/hydroxide (1.5 eq.) was added in a single portion and the 50.6 (CH2) 52.6 (CH2), 53.28 (CH2), 53.3 (CH2), 55.7 (CH2), 55.8
reaction stirred at room temperature for the reported time (CH2), 56.6 (CH2), 80.7 (C), 81.8 (C), 169.9 (C), 170.0 (C), 170.4
(Table 1). 2-Propanol was then evaporated under reduced (C) 177.3 (C). MS (ESI+) calculated for: [C39H73N5O9 + Na]+
pressure and the aqueous phase was washed with CH2Cl2 778.54, found 778.60.
(3 × 5 mL). The organic solvent was dried (Na2SO4), filtered and
evaporated under vacuum to give the corresponding BFCA.
Acknowledgements
General procedure for enzymatic hydrolyses
Methyl ester (6, 11, 15, 200 mg) was added to a suspension of The research leading to these results received funding from
lipase (60 mg) in a mixture of 2.0 mL of phosphate buffer the European Union’s Seventh Framework Programme (FP7/
(1 M, pH 7.5) and 8 mL of methyl t-butyl ether. The reaction 2007-2013) under grant agreement no. HEALTH-F2-2011-
mixture was stirred at room temperature for the reported time 278850 (INMiND). Financial support from Regione Piemonte
(Table 1). The lipase was removed by filtration on a Celite®, (ATHIMAG project) is gratefully acknowledged.
the filtrate was concentrated and the aqueous phase was
extracted with CH2Cl2 (3 × 5 mL). The organic solvent was
dried (Na2SO4), filtered and evaporated under vacuum to give
the corresponding BFCA.
Notes and references
1 (a) E. Alessio, Bioinorganic Medicinal Chemistry, Wiley-VCH,
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Example procedures for gram-scale enzymatic hydrolyses
Methyl ester (6 or 11, 10.0 g) was added to a suspension of
CAL lipase (3.0 g) in a mixture of 10 mL of phosphate buffer
(1 M, pH 7.5) and 40 mL of methyl t-butyl ether. The reaction
mixture was stirred at room temperature for 8 h. The lipase
was removed by filtration on a Celite®, the filtrate was concen-
trated and the aqueous phase was extracted with CH2Cl2
(3 × 25 mL). The organic solvent was dried (Na2SO4), filtered
and evaporated under vacuum to give L1 (9.4 g, 97%) or L2
(9.6 g, 97%).
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Ligand 1. 1H NMR (300 MHz, CDCl3) δ (ppm): 1.22–1.30
(m, 14H, CH2), 1.41 (s, 18H, CH3), 1.42 (s, 18H, (CH3) 1.60 (m,
2H, CH2), 2.31 (t, J = 7.5 Hz, 2H, CH2), 2.62 (d, 2H, J = 14.1 Hz,
(CH2), 2.62–2.68 (m, 2H, CH2), 2.72–2.80 (m, 2H, CH2), 2.98 (d,
2H, J = 14.4 Hz, (CH2), 3.22 (bs, 4H, CH2), 3.61 (bs, 4H, CH2).
13C {1H} NMR (75 MHz, CDCl3) δ (ppm): 22.0 (CH2), 24.7,
(CH2), 28.2 (CH3) 28.3 (CH3), 29.0 (CH2), 29.2 (2 × CH2), 29.4,
30.4 (CH2), 34.1 (CH2), 37.6 (CH2), 51.9 (CH2), 59.3 (CH2), 62.5
(CH2), 63.0 (C), (CH2), 65.4 (CH2), 80.3 (C), 80.8 (C), 170.9 (C),
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173.0 (C), 179.0 (C). MS (ESI+) calculated for: [C39H71N3O10
+
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Ligand 2. 1H NMR (300 MHz, CDCl3) δ (ppm): 1.18–1.31 (m,
14H, CH2), 1.40 (s, 9H, (CH3), 1.41 (s, 18H, (CH3), 1.55 (quint,
J = 7.1 Hz, 2H, CH2) 2.21 (t, J = 7.4 Hz, 2H, CH2), 2.67–2.80 (m,
10H, CH2), 2.88 (m, 8H, CH2), 3.01–3.15 (m, 1H, CH), 3.25 (s,
4H CH2), 3.29–3.37 (m, 2H CH2). 13C {1H} NMR (75 MHz,
CDCl3) δ (ppm): 25.3 (CH2) 25.7 (CH2), 27.9 (CH3), 28.2 (CH3),
29.1 (2 × CH2), 29.2, 29.8 34.9, 36.4 (CH2), 49.6 (CH2), 51.2
(CH2), 52.8 (CH2), 53.1 (CH2), 56.1 (CH2), 56.5 (CH2), 59.7
(CH2), 65.8 (CH), 81.2 (C), 81.4 (C), 170.6 (C), 170.8 (C), 178.7
(C). MS (ESI+) calculated for: [C37H70N4O9 + Na]+ 737.53, found
737.70.
Ligand 3. 1H NMR (300 MHz, CDCl3) δ (ppm): 1.18–1.35 (m,
16H, CH2), 1.44 (s, 9H, (CH3), 145 (s, 18H, CH3), 1.6 (quint, J =
7.2 Hz, 2H, CH2) 2.18 (t, J = 7.5 Hz, 2H, CH2), 2.75–2.88 (br,
18H, CH2), 3.20–3.31 (m, 6H, CH2). 13C {1H} NMR (75 MHz,
CDCl3) δ (ppm): 25.2 (CH2) 26.9 (CH2), 28.0 (CH3), 28.2 (CH3),
29.1 (CH2), 29.2 (2 × CH2), 29.3, 29.6, 28.7, 34.9, 39.5 (CH2),
4926–4936;
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6920 | Org. Biomol. Chem., 2014, 12, 6915–6921
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