Synthesis of Natural Products Combretastatin A-1 and Combretastatin B-1

doi:10.7503/cjcu20130155

Abstract

Abstract:

A new synthetic protocol based on Perkin reaction for access to the antivascular and antitumor natural products combretastatin A-1(CA1) and combretastatin B-1(CB1) was developed. Starting from 2,3,4-trihydroxybenzaldehyde(1), 2,3-dihydroxy-4-methoxybenzaldehyde(2) could be readily obtained via monomethylation, subsequent protection reaction was performed to afford the catechol protected intermediate 2,3-diisopropyloxy-4-methoxybenzylaldehyde(3). Perkin condensation between compound 3 and 3,4,5-trimethoxyphenylacetic acid(4) gave E-2-(3,4,5-trimethoxyphenyl)-3-(2',3'-diisopropyloxy-4'-methoxybenzyl)acrylic acid(E-5) which underwent a decarboxylation reaction to afford Z-2',3'-diiso-propyloxy-3,4,4',5-tetramethoxystilbene(6), and CA1 could then be obtained by deprotection reaction. In addition, E-2-(3,4,5-trimethoxyphenyl)-3-(2',3'-dihydroxy-4'-methoxybenzyl)acrylic acid(7) could be obtained by deprotection reaction, followed by a decarboxylation-isomerization reaction to afford E-combretastatin A-1(E-CA1). Finally, CB1 could be obtained via catalytic hydrogenation.

Key words: Perkin reaction, Combretastatin A-1, Combretastatin B-1, Antitumor

CLC Number:

O629

TrendMD:

LÜ Ze-Liang, HUANG Tong-Kun, NI Qing-Chun, XIAO Chun-Fen, ZOU Yong. Synthesis of Natural Products Combretastatin A-1 and Combretastatin B-1[J]. Chem. J. Chinese Universities, 2013, 34(10): 2313.

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