Chemoenzymatic construction of chiral alkenyl acetylenic alcohol, a key building block to access diastereoisomers of polyacetylenes

Bioresources and Bioprocessing

Table 2 Solvent effect on the optimization of enzymatic kinetic resolution of acetylenic alcohol 3

Entry	Solvent	Log P	t (h)	Conversion (%) ^a	( R )-3 ^b	( S )-11 ^b	E ^c
Entry	Solvent	Log P	t (h)	Conversion (%) ^a	% e.e.	% e.e.	E ^c
1	Dioxane	−1.10	1.5	4	2.2	58.0	4
2	CH₃CN	−0.33	1.5	22	23.3	95.2	51
3	Acetone	−0.23	1.5	15	20.6	80^e	11
4	THF	0.49	1.5	13	10.0	84.5	13
5	Et₂O	0.85	1.5	46.6	78.7	95.0	94
6	^tBuOMe	0.96	1.5	45	76.4	97.0	152
7	Toluene	2.50	1.5	49.3	91.1	96.6	185
8	n-Hexane	3.50	0.5	56	96.0	97.7	340
9	n-Octane	4.50	0.5	51.1	89.0	97.9	284
10	n-Hexane	3.50	6	60.0	96.0	64.2	17
11	n-Octane	4.50	6	54.3	98.4	96.2	300
12	Et₂O	0.85	6	52.9	97.7	89.2	78
13	^tBuOMe	0.96	6	52.4	98.4	91.6	109
14	Toluene	2.50	6	50.3	98.4	97.3	354
15^d	Toluene	2.50	6	50.3	97.4	97.3	319

Reaction conditions: rac-3 (30 mg, 0.1 mmol), Novozym 435 (20 mg, 67% w/w, 1,000 U/mmol), vinyl acetate (62 μL, 6.6 equiv), solvent (1 mL), R.T. ^aConversion (C) was determined by HPLC (Chiralcel AS-H; flow rate: 0.50 mL/min; ⁱPrOH/n-hexane: 1/99; temperature: 25°C; UV: λ = 199 nm); ^bthe determination of enantioselectivity (HPLC Chiralcel AS-H) and the absolute configuration (Mosher's method) of 3 are illustrated in Additional file 1; ^c E = ln[(1 − e.e._S)(1 − C)]/ln[(1 + e.e._S)(1 − C)], where e.e._S represents the enantiomeric excess of the recovered alcohol; ^d257 mg of rac-3 was applied, see the Experimental section for details; ^esince considerable side products were contaminated, the HPLC determination (80% e.e.) of (R)-3 was not calibrated.