【药物名称】
化学结构式(Chemical Structure):
参考文献No.38982
标题:Azetidinone derivs. for the treatment of HCMV infections
作者:Ogilvie, W.W.; O'Meara, J.; Deziel, R.; Yoakim, C. (Boehringer Ingelheim (Canada) Ltd.)
来源:EP 1021405; WO 9918072
合成路线图解说明:

Serine derivative (I) is converted into butyric acid derivative (II) by first treatment with isobutyl chloroformate and Et3N in THF, followed by reaction with ethereal diazomethane, Wolf rearrangement with Et3N in THF/H2O catalyzed by AgOBz and benzylation with benzyl bromide and DBU in acetonitrile. Conversion of (II) into azetidinone derivative (III) is achieved by Boc group removal by means of HCl in dioxane followed by cyclization by treatment with TMSCl, Et3N in Et2O and then t-BuMgCl. Protection of (III) using TIPSOTf and 2,5-lutidine in CH2Cl2 followed by removal of benzyl ether by hydrogenolysis over Pd(OH)2 in THF gives beta-lactam alcohol (IV), which is then oxidized by means of Dess-Martin periodinane in CH2Cl2 to yield aldehyde (V). Reaction of (V) with benzothiazole (VI) and n-BuLi in THF yields alcohol (VII), which is then deoxygenated by treatment with 1,1-(thiocarbonyl)diimidazole and DMAP in CH2Cl2 followed by reduction with Ph3SnH and AIBN in benzene to afford (VIII). Removal of the TIPS group from (VIII) by means of CsF in MeOH followed by condensation with chloride (IX) by means of KHMDS in THF finally furnishes the target product.

参考文献No.546932
标题:Synthesis and antiviral activity of monobactams inhibiting the human cytomegalovirus protease
作者:Ogilvie, W.W.; Yoakim, C.; D? F.; Hach? B.; Lagac? L.; Naud, J.; O'Meara, J.A.; D閦iel, R.
来源:Bioorg Med Chem 1999,7(8),1521
合成路线图解说明:

Serine derivative (I) is converted into butyric acid derivative (II) by first treatment with isobutyl chloroformate and Et3N in THF, followed by reaction with ethereal diazomethane, Wolf rearrangement with Et3N in THF/H2O catalyzed by AgOBz and benzylation with benzyl bromide and DBU in acetonitrile. Conversion of (II) into azetidinone derivative (III) is achieved by Boc group removal by means of HCl in dioxane followed by cyclization by treatment with TMSCl, Et3N in Et2O and then t-BuMgCl. Protection of (III) using TIPSOTf and 2,5-lutidine in CH2Cl2 followed by removal of benzyl ether by hydrogenolysis over Pd(OH)2 in THF gives beta-lactam alcohol (IV), which is then oxidized by means of Dess-Martin periodinane in CH2Cl2 to yield aldehyde (V). Reaction of (V) with benzothiazole (VI) and n-BuLi in THF yields alcohol (VII), which is then deoxygenated by treatment with 1,1-(thiocarbonyl)diimidazole and DMAP in CH2Cl2 followed by reduction with Ph3SnH and AIBN in benzene to afford (VIII). Removal of the TIPS group from (VIII) by means of CsF in MeOH followed by condensation with chloride (IX) by means of KHMDS in THF finally furnishes the target product.

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