RS-135853

Chemical Name: (1R,3aR,4S,4aR,7R,7aR,8aS)-4-Formyl-3-isopropyl-8a-[(2R,6S,7R)-6-methoxy-7-methyl-4-(2-methyl-2-propenyl)perhydro-1,4-oxazepin-2-yloxymethyl]-7-methyl-4,4a,5,6,7,7a,8,8a-octahydro-1H-1,4-methano-s-indacene-3a-carboxylic acid
项目整合开发状态: Preclinical
项目研究机构: Sankyo (Originator)
合成路线:The hydrolysis of Zofimarin (I) with NaOMe in methanol gives the sodium salt of the deacylated compound (II),which is treated with Pmb-Cl in DMF to yield the p-methoxybenzyl ester (III).The protection of the formyl group of (III) by means of ethyleneglycol,trimethyl orthoformate and TsOH affords the ethylene ketal (IV),which is oxidized at the vicinal diol group by means of NaIO4 in methanol/water to provide the dialdehyde (V).The reductocyclization of (V) with allylamine (VI) by means of NaBH3CN and AcOH in acetonitrile leads to the perhydro oxazepine derivative (VII),which is deallylated by means of Rh(PPh3)3Cl in aqueous ethanol to give compound (VIII).The alkylation of (VIII) with 2-methylallyl bromide (IX) by means of NaHCO3 and NaI in ethanol yields the protected precursor (X),which is finally treated with TFA in dichloromethane to provide the target zofimarin derivative.