Abstract:
(S)-4-Hydroxy-a-lapachone has been prepared for the first time.
The commercially available compound 2-acetyl-1-naphthol was used
as the starting material. The synthesis involved methylation,
followed by Baeyer-Villiger oxidation, and hydrolysis of the acetate
to give 1-methoxy-2-naphthol. After protecting of the hydroxyl
group, t-BuLi was used to form 3-(3',3'-dimethyl-acryloyl)-1-
meth oxy-2- (meth oxymethoxy)-naphthalen e. eycl izationand
oxidation then gave 4-keto-a-lapachone. Finally enzymic
biotransformation by Mortierella isabellina ATCC 42613 was used
to yield the target compound. The enantiomeric excess of the product
was determined to be ~98% by using 1H NMR chiral shift analysis. The
overall yield is 80/0. The biological activity of (S)-4-hydroxy-alapachone
and its acetate are under investigation.
