A new synthetic protocol for access to the antivascular and antitumor natural product combretastatin B-1(CB1) has been developed. Starting from isovanillin(1), 2-bromo-3-hydroxy-4-methoxybenzaldehyde (2) could be readily obtained via bromination with DBDMH. Perkin condensation between 2 and 3, 4, 5-trimethoxyphenylacetic acid (3) gave Z/E-2-(3, 4, 5-trimethoxyphenyl)-3-(2-bromo-3-acetoxy-4-methoxyl) acrylic acid (Z-4, E-4), which underwent hydroxylation and the tandem decarboxylation-isomerization reactions to afford E-combretastatin A-1 (E-CA1). Finally, CB1 could be obtained by catalytic hydrogenation.