ASYMMETRIC SYNTHESIS OF (S, S, R)-(-)-ACTINONIN AND ITS ANALOGS AND USES THEREFOR

摘要

The present invention provides methods for the asymmetric synthesis of (S.S.R)-(-)-actinonin and its analogs and the compounds thereby synthesized having a structural formula: where R<1> is an optionally substituted or halogenated alkyl, aryl, heteroalyl or heteroaryl amine, said R<1> further comprising a cyclie or bicyclic structure; R2 is methyl, CH2CH3, (CH2)2CH3, C(CH3)3, phenyl, 3, 4-dichlorophenyl, biphenyl, benzyl, 4-hydroxybenzyl, piperidine, N-Boc-4-piperidine, CH2-(N-Boc-4-piperidine), 4-tetrahydropyran, CH2-4-tetrahydropyran. 3-methyl indolyl, 2-napythyl, 3-pyridyl, 4-pyridyl, 3-thienyl; R<3> is R<2> or C3-8alkyl, R<4> is C1-3alkyl; and R<5> is NH2, OH, NHOH, NHOCH3, N(CH3)OH, N(CH3)OCH3, NHCH2CH3, NH(CH2C H 3), NHCH2(2, 4-(OCH3)2pH, NHCH2(4-NO2)Ph, NHN(CH3)2, proline, or 2-hydroxymethyl pyrrolidine. Additionally, a method for the treatment of a neoplastic disease or for the inhibition of tumor cell growth each comprising the step of administering to an individual in need of such treatment a pharmacologically effective dose of the compounds of the present invention are provided.