新产品编号:1897327

Chemical Name: (1R,2R,3aR,3bS,5R,8S,11S,14S,16R,18R,19aS,20aS,22S,23R,24aS,25S,25aR,29R,30aS,31S,32aR)-22-Hydroxy-23-(hydroxymethyl)-16,25-dimethyl-10,15-dimethylideneperhydro-1,5:8,11,14,18-triepoxy-29,31-ethano-2,5-methanofuro[2',3':5,6]pyrano[4,3-b]pyrano[2',3':5,6]p
项目整合开发状态: Biological Testing
项目研究机构: Eisai (Originator)
合成路线:Dess-Martin oxidation of alcohol (I) in CH2Cl2 yields aldehyde (II),which is then subjected to a Horner-Emmons reaction with phosphonate (III) in THF in the presence of NaH to provide compound (IV).Enone (IV) is then converted into intermediate (V) by first conjugate reduction by the Stryker reagent,reduction with NaBH4 in MeOH of the resulting saturated ketone,separation of the two possible diastereomers obtained and final mesylation by means of Ms2O and Et3N.Dess-Martin oxidation of the primary alcohol (VI) affords aldehyde (VII),which is then coupled to mesylate (V) by means of NiCl2-CrCl2 in DMF/THF.The resulting product is subjected to cyclization by means of KH in DME to furnish tetrahydropyran derivative (VIII).Reduction of (VIII) with LiAlH4 in Et2O yields alcohol (IX),which is then oxidized by the Dess Martin reagent to give aldehyde (X).Coupling of (X) with compound (XI) by means of NiCl2-CrCl2 in DMF/THF affords ketone (XII).

合成路线:The next steps for conversion of (XII) into (XIII) are: Dess-Martin oxidation,removal of the (p-methoxyphenyl)methyl group (MPM) by means of DDQ in phosphate buffer/tert-BuOH/CH2Cl2,hydrolysis of the methyl ester with LiOH in H2O/THF and,finally,Yamaguchi lactonization.Finally,the target product is obtained by removal of the TBDMS groups of lactone enone (XIII) with tetrabutyl ammonium fluoride (TBAF) in THF to furnish alcohol (XIV),followed by treatment with p-TsOH.Py (PPTS) in CH2Cl2,activation with p-nitrobenzoyl chloride in CH2Cl2 in the presence of pyridine,reaction with TBSOTf and Et3N in CH2Cl2,and final saponification with K2CO3 in MeOH.