ChemInform Abstract: SYNTHESIS OF L‐EPICAPREOMYCIDINE

Abstract

Der aus (I) dargestellte Aldehyd (III) kondensiert sich mit dem Cu‐Komplex (IV) zu den Isomeren (V).

Studies on the biosynthesis of clavulanic acid. Part 4. Synthetic routes to the monocyclic β-lactam precursor, proclavaminic acid

“…The resulting adduct (15) was successfully reduced and deprotected in a one-step catalytic hydrogenation to give the required compound (2) as a solid in quantitative yield. The aldol reaction consistently produced the product (15) as a mixture of diastereoisomers in the approximate ratio 2: 3. Trituration of the mixture of diastereoisomers (2) with methanol dissolved all the minor diastereoisomer and some of the major diastereoisomer, leaving the bulk of the major component as a diastereoisomerically pure solid.…”

“…This material was used without further purification; 6,(250 MHz; [2H6]DMSO-D20) 1.561.79 (2 H, m, 4-H,), 2.89 (2 H, t, J2.9, 3'-H,), 3.28-3.53 (4 H, m, 5-and 4'-H,), 3.89 (1 H, m, 3-H), and 4.10 (1 H, d, J6.6,2-H). (15) (950 mg, 2.98 mmol), prepared by aldol coupling, was dissolved in DCM (100 ml) and the solution was stirred with DBN (0.37 g, 2.98 mmol) for 1.5 h at room temperature. The reaction mixture was evaporated under reduced pressure and chromatographed with DCM-ethyl acetateethanol (60: 10: 1) as eluant to give the faster running threobenzyl 5-azido-3-hydroxy-2-(2-oxoazetidin-1 -yl)valerate (15) (370 mg, 39%) as an oil which solidified after a time, m.p.…”

“…oxoazetidin-1-yf)uaferate(15) as an oil (0.95 g, 7473, vma,(KBr) 3 407 (OH), 2 100 (N3), and 1733 cm-' (CO);6,(250 MHz) 1.661.84 (1 H, m) and 1.88-2.04 (1 H, m) (4-H), 2.99 (2 H, t, J 4.2, superimposed upon m, 3'-H2), 3.263.38 (2 H, m, 4'-H2), 3.39-3.53 (2 H, m, 5-H,), 4.03 (1 H, d, J3.3,2-H), 4.22430 (1 H, m, 3-H), 4.51 (1 H, d, J 4.5, OH, exch. D,O), 5.23 (2 H, s, CH,Ph), and 7.34 (5 H, s, Ph); m/z (FAB, thioglycerol) (Found: M H + , 319.1397.…”

“…2S,3R)-Benzyl 5-Azido-3-hydroxy-2-(2-oxoazetidin-1 -yl)ualerate(15)-Finely powdered threo-benzyl 5-azido-3-hydroxy-2-(2-oxoazetidin-l-yl)valerate(15) (2 g, 6.3 mmol) was suspended in water (1 1) and the mixture was stirred at 36 "C with subtilisin Carlsberg (EC 3.4.21.14) (400 units) while the pH was maintained at 6.5 by the addition of 1wNaOH. After 5.5 h, after alkali (3.7 ml) had been added, the reaction mixture was extracted three times with DCM.…”

“…The extracts were bulked, dried, and evaporated under reduced pressure. The residual oil (1.25 g) was chromatographed with ethyl acetate-hexaneethanol (20: 30: 1) as eluant to give (2S,3R)-benzyl 5-azido-3hydroxy-2-(2-oxoazetidin-l-yl)ualerate(15) (0.78 g, 78%) as an oil, [ a ] ; ' + 33.15" (c 2.0, CHCI,); vmax 2 100 (N3), 1 724br (CO and CO,), 753, and 699 cm-l; 6,(250 MHz) 1.60-1.95 (2 H, m, 4-H,), 2.95-3.15 (2 H, m, 3'-H,), 3.31-3.19 (1 H, m) and 3.40-3.48 (1H,m)(4'-H,),3.51(2H,dd,J7.4and5.6,5-H2),4.03(1H,d,J 2.9, OH), 4.25-4.40 (2 H, m, 3-and 2-H), 5.22 and 5.26 (2 H, ABq, J 12, CH,Ph), and 7.31 (5 H, s, Ph); addition of (S)-1-(9-anthryl)-2,2,2-trifluoroethanol to the NMR solution demonstrated the presence of a single enantiomer; m/z (FAB, thioglycerol) (Found: M H + , 319. C1 5H19N404 requires m/z, 319); CD in MeCN A ~2 1 5 +2.7, AE242.9 -0.088, and -0.005.5-Amino-3-hydroxy-2-(2-oxoazetidin-1-yl)ualericAcid (2) by Catalytic Reduction of Azide (14).-5-Azido-3-hydroxy-2-(2oxoazetidin-1-y1)valeric acid (14) (58 mg, 0.25 mmol) was dissolved in a mixture of ethanol (4 ml) and water (2 ml), and hydrogenated with 5% Pd-carbon catalyst at ambient temperature for 1 h. After filtration and evaporation, the resulting gum was triturated with ether to give 5-amino-3-hydroxy-2-(2oxoazetidin-1-y2)ualeric acid (2) as a white solid (47.6 mg, 93%) (Found: C, 46.7; H, 7.6; N, 11.0.…”