Preparation of chiral hydroxyester synthons vis stereoselective porcine pancreatic lipase-catalysed hydrolyses of meso-diesters

Abstract

Stereoselective porcine pancreatic lipase-catalysed hydrolyses of monocyclic rneso-I ,2-diesters provides a flexible and convenient preparative route t o chiral hydroxyesters and lactones of asymmetric synthetic value.The abilities of enzymes to catalyse stereospecific transformations of meso-compounds into chiral synthons pf asymmetric synthetic value are becoming increasingly well documented. 1 Horse liver alcohol dehydrogenase (HLADH)2.3 and pig liver esterase (PLE)4,5 have proven particularly valuable in this regard. In view of the increasing interest in this area, and the exciting results reported by other gr0ups6~7 using porcine pancreatic lipase (PPL, EC 3.1.1.3), we have evaluated the stereospecificity of PPL-catalysed hydrolyses of the monocyclic meso-diesters (1)-( 4). f We t The substrate diesters (1)-(4) were readily prepared from their known precursor diols.3 All new compounds gave satisfactory spectral and elemental analytical data.

Peptide Synthesis in Organic Solvents Catalyzed by an Industrial Alkaline Protease “Alcalase”

“…PPL is an inexpensive enzyme from crude pancreatic lipase" and is widely used for its broad substrate specificity and stability in organic solvents. 32 -34 Fig. 7 shows the time course for a1calase-catalysed synthesis of hydroxamates from each of the corresponding peptide esters of Cbz-Ala-Asp(Bzl)-Phe-, Moz-Thr(Bzl)-Leu-, and Boc-Pro-Phe-Leu-, and hydroxyamine.…”

Ugi and Passerini Reactions of Biocatalytically Derived Chiral Aldehydes: Application to the Synthesis of Bicyclic Pyrrolidines and of Antiviral Agent Telaprevir

“…1 H NMR (CDCl 3 , 25 °C): δ = 3.54−3.67 (m, 2 H, CH 2 OH), 3.29 and 3.45 (AB part of an ABX system, J AB = 12.3, J AX = 6.9; J BX = 7.8 Hz, 2 H, CH 2 N 3 ), 2.28 (hexuplet, J = 7.2 Hz, H-1 or H-2), 2.22 (center of m, 1 H, H-1 or H-2), 1.31−1.90 (m, 7 H). 13 (10), 95 (5.3), 86 (5.1), 82 (19), 81 (41), 80 (10), 79 (29), 77 (5.7), 70 (9.7), 69 (25), 68 (23), 67 (100), 66 (9.0), 65 (7.8), 59 (68), 57 (20), 56 (73), 55 (25), 54 (37), 53 (21), 46 (15), 43 (18), 42 (14) was added dropwise, and the solution was stirred for 10 min at −78 °C. Triethylamine (2.10 mL, 15.13 mmol) was then added, and the solution was stirred for 1 h at the same temperature.…”

“…1 H NMR (CDCl 3 , 29 °C): δ = 5.95 (br t, J = 6.0 Hz, 1 H, NHBu), 5.20 (d, J = 6.3 Hz, 1 H, CHOCOEt), 3.45 and 3.19 (AB part of a ABX syst., J AB = 12.3, J AX = 6.9, J BX = 8.1 Hz, 2 H, CH 2 N 3 ), 3.26 (dt, J = 7.2, 6.0 Hz, 2 H, NH−CH 2 ), 2.54 (quintuplet, J = 7.2 Hz, 1 H, H-1), 2.44 (q, J = 7.5 Hz, 2 H, CH 2 CO), 2.33 (sextuplet, J = 6.9 Hz, 1 H, H-2), 1.87−1.43 (m, 8 H, H-3, H-4, H-5, CH 2 of Bu), 1.37−1.26 (m, 2 H, CH 2 of Bu), 1.19 (t, J = 7.5 Hz, 3 H, COCH 2 CH 3 ), 0.92 (t, J = 7.2 Hz, 3 H, CH 3 of Bu). 13 (19), 132 (5.3), 131 (75), 130 (13), 126 (31), 110 (16), 109 (11), 108 (14), 100 (13), 96 (7.7), 82 (7.5), 81 (22), 80 (8.3), 79 (9.0), 74 (7.9), 67 (9.8), 59 (8.9), 58 (8.0), 57 (100), 56 (8.7), 55 (7.0), 41 (18)…”

“…1 H NMR (CDCl 3 , 29 °C): δ = 7.32 (br t, J = 4.8 Hz, 1 H, NHCOEt), 7.09 (br t, J = 5.7 Hz, 1 H, NH-Bu), 4.90 (d, J = 5.7 Hz, 1 H, OH), 4.18 (t, J = 5.4 Hz, 1 H, CHOH), 3.48 (ddd, J = 13.8, 8.4, 5.7 Hz, 1 H, CHH-NHCOEt), 3.30 (dt, J = 13.2 (d), 6.9 (t) Hz, 1 H, NHCH 2 -Pr), 3.23 (dt, J = 13.2 (d), 6.9 (t) Hz, 1 H, NHCH 2 -Pr), 3.11 (dt, J = 13.8 (d), 4.8 (t) Hz, 1 H, CHH-NHCOEt), 2.26 (center of m, 2 H, H-1 and H-2), 2.18 (q, J = 7.5 Hz, 2 H, CH 2 CO), 1.83−1.29 (m, 10 H, H-3, H-4, H-5, 2 CH 2 of Bu), 1.12 (t, J = 7.5 Hz, 3 H, COCH 2 CH 3 ), 0.93 (t, J = 7.2 Hz, 3 H, CH 3 of Bu). 13 GC-MS (initial temp: 70 °C): R t = 11.17 min; m/z 284 (M + , 8.0%), 184 (40), 156 (11), 155 (30), 154 (7.3), 131 (29), 128 (13), 126 (21), 111 (21), 110 (49), 100 (16), 98 (7.3), 94 (5.8), 93 (11), 91 (6.1), 87 (43), 86 (15), 81 (13), 79 (7.2), 75 (5.2), 74 (100), 72 (5.1), 70 (5.8), 69 (5.5), 67 (14), 59 (5.2), 58 (9.7), 57 (62), 56 (10), 55 (14), 44 (12), 43 (7.5), 41 (25) ( GC-MS (initial temp: 70 °C): R t = 11.25 min; m/z 284 (M + , 5.6%), 210 (6.2), 185 (9.5), 184 (78), 182 (7.4), 156 (8.3), 155 (23), 154 (13), 131 (52), 128 (21), 126 (19), 111 (34), 110 (86), 100 (20), 98 (11), 94 (6.0), 93 (17), 87 (34), 86 (15), 81 (18), 79 (9.6), 77 (5.3), 75 (5.2), 74 (100), 72 (7.4), 70 (7.6), 69 (7.0), 67 (19), 59 (7.1), 58 (12), 57 (86), 56 (15), 55 (19), 53 (5.7), 44 (13), 43…”

“…The mixture was stirred for 3 h at 0 °C, then treated with saturated aq NH 4 Cl solution ( Hz, 1 H, CHNHBoc), 3.74 and 3.17 (AB part of an ABX system, J AB = 12.0, J AX = 9.3, J BX = 5. 4 (11), 108 (5.4), 100 (14), 98 (6.6), 97 (8.0), 96 (8.2), 82 (8.4), 81 (40), 80 (6.5), 79 (16), 74 (14), 72 (5.8), 70 (5.8), 69 (13), 68 (7.5), 67 (19), 59 (27), 58 (19), 57 (41), 56 (15), 55 (18)…”