Total Syntheses and Biological Evaluation of Both Enantiomers of Several Hydroxylated Dimeric Nuphar Alkaloids.

ABSTRACT: Herein, we describe the first total syntheses of five members of the dimeric nuphar alkaloids: (+)-6,6'-dihydroxythiobinupharidine (+)-1?a, (+)-6-hydroxythiobinupharidine (+)-1?b, (-)-6,6'-dihydroxythionuphlutine (-)-2?a, (-)-6,6'-dihydroxyneothiobinupharidine (-)-3?a, and (+)-6,6'-dihydroxyneothionuphlutine (+)-4?a. The latter two have not been found in nature. We have also made each of their enantiomers (-)-1?a-b, (+)-2?a, (+)-3?a, and (-)-4?a. The key step in these syntheses was the dimerization of an ?-aminonitrile (a hydrolytically stable surrogate for its corresponding hemiaminal) with chiral Lewis acid complexes. We have also reassigned the literature structures of (+)-1?a-1?b—for those instances in which the NMR spectra were obtained in CD3OD—to their corresponding CD3O-adducts. Our efforts provide for the first time apoptosis data for (-)-3?a, (+)-4?a, and all five non-natural enantiomers prepared. The data indicate high apoptotic activity regardless of the enantiomer or relative stereochemical configuration at C7 and C7'.

SUBMITTER: Korotkov A 

PROVIDER: S-EPMC4691328 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature