新产品编号:1772349

Chemical Name: (1R,5S,6S)-6-[1(R)-Hydroxyethyl]-2-[5(S)-[3-(hydroxymethyl)-4,5-dihydroisoxazol-5-yl]pyrrolidin-3(S)-ylsulfanyl]-1-methyl-1-carba-2-penem-3-carboxylic acid isomer 1
项目整合开发状态: Biological Testing
项目研究机构: LG Chem (Originator)
合成路线:Treatment of trans-4-hydroxy-L-proline (I) with p-nitrobenzyl chloroformate gave the N-protected 4-hydroxyproline (II),which was esterified to afford the N-protected methyl ester (II).Protection of the hydroxyl group of (III) with t-butyl-dimethylsilyl chloride in the presence of imidazole,followed by reduction of the resulting ester (IV) with lithium borohydride,provided the alcohol (V).This was oxidized using pyridine-sulfur trioxide complex to give the formylpyrrolidine (VI).The vinylpyrrolidine (VII) was obtained by Wittig reaction of aldehyde (VI) with methylene triphenylphosphorane.Dipolar cycloaddition of the nitrile oxide resulting from ethyl chlorooximidoacetate (VIII) and Et3N to vinylpyrrolidine (VII) gave iso-oxazolidine (IX) as a mixture of diastereoisomers.After desilylation of (IX) with tetrabutylammonium fluoride,the resulting alcohol (X) was converted into the diastereomeric mixture of mesylates (XI).Chromatographic separation of the required isomer,followed by reduction with LiBH4,yielded alcohol (XII).

合成路线:Displacement of the mesylate group of (XII) with potassium thioacetate gave thioester (XIII),which was further hydrolyzed to thiol (XIV).This was condensed with enol phosphate (XV) to afford the protected 1-methylcarbapenem (XVI).Finally,deprotection of the p-nitrobenzyl groups of (XVI) by zinc powder in the presence of phosphate buffer (pH 6.0) provided the title compound.