5-(dithiolan-3-yl)pentanamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl (2RS) (+/−) 2-ethoxy-3-(4-hydroxyphenyl)propanoate in t-butyl ethyl ether (dried on 3 Å molecular sieve) (10 mg/ml) was added n-hexanol (2 equivalents), triethylamine (dried on 3 Å molecular sieve) (14 mol %), 4 Å molecular sieve, and Mucor miehei lipase Lipozyme IM (from Novo Nordisk) (20 mg). The reaction mixture was shaken at room temperature and analysed at different times. The reaction mixture was analysed by the gradient HPLC method 1 and by the chiral CE method 2.

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: heating to 70°C. Thereto were added 10 parts by weight of an immobilized lipase preparation (trade name: Lipozyme, IM20, mfd. by NOVO) composed of a lipase originating from Mucor miehei immobilized on an anion exchange resin and 29 parts by weight of linear diglycerol. Then the stearic acid was reacted with the linear glycerol under reduced pressure (2 torr) at 70° C. for 4 hours. The reaction product was filtered to eliminate the immobilized enzyme. The obtained filtrate was put in a continuous thin film distilling apparatus and distillation was carried out to eliminate unreacted stearic acid and diglycerol, and monoesters. The liquid thus obtained was subjected to silica gel column chromatography to eliminate triesters, thereby giving a diglycerol distearate mixture comprising diglycerol 1,6-distearate (about 50%), diglycerol 1,5-distearate (about 45%) and diglycerol 2,5-distearate (about 5%). Thereto were added 10 parts The reaction product was filtered distilling apparatus and distillation The liquid thus obtained

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: heating to 70°C. Thereto were added 10 parts by weight of an immobilized lipase preparation (trade name: Lipozyme, IM20, mfd. by NOVO) composed of a lipase originating from Mucor miehei immobilized on an anion exchange resin and 29 parts by weight of linear diglycerol. Then the stearic acid was reacted with the linear glycerol under reduced pressure (2 torr) at 70° C. for 4 hours. The reaction product was filtered to eliminate the immobilized enzyme. The obtained filtrate was put in a continuous thin film distilling apparatus and distillation was carried out to eliminate unreacted stearic acid and diglycerol, and monoesters. The liquid thus obtained was subjected to silica gel column chromatography to eliminate triesters, thereby giving a diglycerol distearate mixture comprising diglycerol 1,6-distearate (about 50%), diglycerol 1,5-distearate (about 45%) and diglycerol 2,5-distearate (about 5%). Thereto were added 10 parts The reaction product was filtered distilling apparatus and distillation The liquid thus obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl (2RS) (+/−) 2-ethoxy-3-(4-hydroxyphenyl)propanoate in t-butyl ethyl ether (dried on 3 Å molecular sieve) (10 mg/ml) was added n-hexanol (2 equivalents), triethylamine (dried on 3 Å molecular sieve) (14 mol %), 4 Å molecular sieve, and Mucor miehei lipase Lipozyme IM (from Novo Nordisk) (20 mg). The reaction mixture was shaken at room temperature and analysed at different times. The reaction mixture was analysed by the gradient HPLC method 1 and by the chiral CE method 2.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl (2RS) (+/−) 2-ethoxy-3-(4-hydroxyphenyl)propanoate in t-butyl ethyl ether (dried on 3 Å molecular sieve) (10 mg/ml) was added n-hexanol (2 equivalents), triethylamine (dried on 3 Å molecular sieve) (14 mol %), 4 Å molecular sieve, and Mucor miehei lipase Lipozyme IM (from Novo Nordisk) (20 mg). The reaction mixture was shaken at room temperature and analysed at different times. The reaction mixture was analysed by the gradient HPLC method 1 and by the chiral CE method 2.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Preparation of hexadecyl cis-10-tetradecenoate, 8 was carried out according to the Scheme 2. Methyl undecenoate, 5 (10.21 g, 0.0515 mol) in dichloromethane (150 ml) was cooled to −78° C. and ozone gas was bubbled into the reaction mixture for 1 hr. The reaction was quenched by adding dimethyl sulphide (DMS, 5 ml) and was stirred for 6 hr at 25° C. The solvents were removed under vacuum and the residue 6 thus obtained was used directly further preparation of cis-10-myristoleate, 7. n-Butyl-triphenyl phosphonium bromide salt (10.0 g, 0.0251 mol) was taken in dry THF (50 ml) and cooled to 0° C. To this slurry, n-Butyl lithium (17.0 ml, 1.6 M in hexane) was added and stirred for 0.5 hr. 1-Al-methyl deaconate containing crude product 6 (5.01 g, 0.025 mol) dissolved in dry THF (50 ml) was added slowly to the above contents and allowed the reaction mixture to warm to roam temperature and then heated to reflux temperature to reflux for 4 hr. THF was removed from the reaction product under reduced pressure, and to the residue distilled water (25 ml) was added and extracted with ether (25 ml×3 times). The combined ether layer was dried over anhydrous sodium sulphate and solvent was evaporated and dried under vacuum to get the product and was further purified by column chromatography using hexane and ethyl acetate (98:2) as eluent to obtain cis-10-myristoleate, 7 (3.35 g, 0.014 mol) in 56% yield with 97% purity by GC. cis-10-Myristoleate, 7 (3.35 g, 0.014 mol) was enzymatically transesterified with cetyl alcohol (4.07 g, 0.0168 mol) in the presence of Lipozyme TL IM (0.745 g, 10 wt % of the total substrate), at 65° C. for 8 hr. The reaction was monitored by TLC and after completion of reaction, hexane (50 ml) was added and the lipase, was separated by filtration and the solvent was evaporated to get the crude product and was purified by column chromatography to obtain hexadecyl cis-10-tetradecenoate, 8 (5.55 g, 0.0123) in 88% yield with 95% purity by GC. The structure of hexadecyl cis-10-tetradecenoate, 8 was confirmed by 1H NMR, IR, and GC-MS. at 65° C. for 8 hr was added the lipase, was separated by filtration the solvent was evaporated to get the crude product was purified by column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Preparation of hexadecyl cis-9-tetradecenoate, 4 was carried out according to the Scheme 1. Oleic acid methyl ester, 1 (12.0 g, 0.0314 mol) in dichloromethane (100 ml) was cooled to −78 degree. C and ozone gas was bubbled into the reaction mixture for 1 hr. After reaction, the reaction was quenched by adding dimethyl sulphide (DMS, 8 ml) and was stirred for 6 hr at 25° C. The solvents were removed under vacuum and the residue 2 thus obtained (4.25 g, 0.022 mol) was used directly for the preparation of cis-9-myristoleate, 3. n-Pentyl-triphenyl phosphonium salt (11.16 g, 0.027 mol) was taken in 50 ml of dry THF and cooled to 0° C. To this slurry, n-butyl lithium (17.0 ml, 1.6 M in hexane) was added, stirred the reaction mixture for 0.5 hr to obtain an orange solution. 1-Al-methyl nonanoate containing crude product 2 (5.0 g, 0.027 mol) dissolved in dry THF (20 ml) was added to the above contents slowly and allowed the reaction mixture to reach to 25 degree. C and then heated to reflux temperature to reflux for 4 hr. The reaction was monitored by TLC and after completion of the reaction, THF was removed from the reaction mixture under reduced pressure, and to the residue distilled water 825 ml) was added and extracted with ether (25 ml×3 times). The combined ether layer was dried over anhydrous sodium sulphate and solvent was removed and dried under vacuum to get the residue and was purified by column chromatography using hexane and ethyl acetate (98:2) as eluent to get cis-9-myristoleate, 3 (4.2 g, 0.0175 mol) in 65% yield with 66% purity by GC. cis-9-Myristoleate, 3 (4.2 g, 0.0175 mol) was enzymatically transesterified with cetyl alcohol (5.08 g 0.021-mol) in the presence of Lipozyme TL IM (0.930 g, 10 wt % of the total substrate) at 68° C. for 8 hr. The reaction was monitored by TLC and after completion of the reaction, hexane (50 ml) was added and the lipase was separated by filtration and the solvent was evaporated to get the crude product and was purified by column chromatography to obtain hexadecyl cis-9-tetradecenoate, 4 (7.48 g, 0.0166 mol) in 95% yield with 92% purity by GC. The structure of hexadecyl cis-9-tetradecenoate, 4 was confirmed by 1H NMR, IR, and GC-MS. at 68° C. for 8 hr was added the lipase was separated by filtration the solvent was evaporated to get the crude product was purified by column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of isopropyl α-D-glucopyranoside (1.1 g, 5 mmol) and octanoic acid (0.9 g, 6.25 mmol) in 100 ml 2-butanone was added immobilized lipase (0.5 g Lipozyme™, see example 8). Stirring was continued at 60° C. for 48 hours. The enzyme was removed by filtration and the solvent was removed in vacuo followed by chromatography yielding 1.2 g (70%) of the product 1H NMR (400 MHz, CDCl3) δ: 0.88 (t, J=6.7 Hz, 3H); 1.19 (d, J=6.1 Hz, 3H); 1.24 (d, J=6.2 Hz, 3H); 1.28 (m, 8H); 1.62 (m, 2H); 2.34 (m, 2H); 3.35 (t, J=9.4 Hz, 1H); 3.50 (dd, J=4.0 and 9.5 Hz, 1H); 3.73 (t,J=9.3 Hz, 1 H); 3.85 (m, 1H); 3.92 (m, 1H) 4.35 (m, 2H); 4.96 (d, J=3.9 Hz, 1H). The enzyme was removed by filtration the solvent was removed in vacuo

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution (380 mL) of ethyl 3-hydroxy-3,6-dihydro-2H-pyran-4-carboxylate (91.2 g) in diisopropyl ether were added vinyl hexanoate (150 mL) and Lipozyme IM (4.8 g). The reaction mixture was stirred at 35° C. for 24 hr and the insoluble material was filtered off. The obtained filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane/ethyl acetate=6:1→1:1) to give the title compound (45.9 g, 50%). the insoluble material was filtered off The obtained filtrate was concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In accordance with at least one other embodiment of the present technology, glycerol can be treated with ethyl acetoacetate in presence of a lipase at from about 55° C. to about 70° C., alternatively from about 20 to about 75, for approximately 14 to 48 hours, alternatively 20 to 36 hours. The lipase can be, for example, Novozyme® 435, Lipozyme® RM IM, or Lipozyme® TL IM, all available from Novozymes A/S, Franklinton, N.C. The reaction can be performed in an inert (e.g., nitrogen) atmosphere. During the reaction, ethyl alcohol by-product can be removed, for example, via distillation. At the end of the reaction, the remaining ethyl acetoacetate can be removed through distillation (e.g., at 60° C., 1 mmHg). The structure of the triglyceride of acetoacetin produced can be confirmed through, for example, NMR analysis and/or GC. The reaction At the end of the reaction the remaining ethyl acetoacetate can be removed through distillation (e.g., at 60° C., 1 mmHg)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: heating to 70°C. Thereto were added 10 parts by weight of an immobilized lipase preparation (trade name: Lipozyme, IM20, mfd. by NOVO) composed of a lipase originating from Mucor miehei immobilized on an anion exchange resin and 29 parts by weight of linear diglycerol. Then the stearic acid was reacted with the linear glycerol under reduced pressure (2 torr) at 70° C. for 4 hours. The reaction product was filtered to eliminate the immobilized enzyme. The obtained filtrate was put in a continuous thin film distilling apparatus and distillation was carried out to eliminate unreacted stearic acid and diglycerol, and monoesters. The liquid thus obtained was subjected to silica gel column chromatography to eliminate triesters, thereby giving a diglycerol distearate mixture comprising diglycerol 1,6-distearate (about 50%), diglycerol 1,5-distearate (about 45%) and diglycerol 2,5-distearate (about 5%). Thereto were added 10 parts The reaction product was filtered distilling apparatus and distillation The liquid thus obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl (2RS) (+/−) 2-ethoxy-3-(4-hydroxyphenyl)propanoate in t-butyl ethyl ether (dried on 3 Å molecular sieve) (10 mg/ml) was added n-hexanol (2 equivalents), triethylamine (dried on 3 Å molecular sieve) (14 mol %), 4 Å molecular sieve, and Mucor miehei lipase Lipozyme IM (from Novo Nordisk) (20 mg). The reaction mixture was shaken at room temperature and analysed at different times. The reaction mixture was analysed by the gradient HPLC method 1 and by the chiral CE method 2.