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Total Synthesis and Cytotoxic Activity of 5′‐Hydroxyzearalenone and 5′β‐Hydroxyzearalenone
Author(s) -
Thiraporn Aticha,
Rukachaisirikul Vatcharin,
Iawsipo Panata,
Somwang Tatiyar,
Tadpetch Kwanruthai
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201701272
Subject(s) - chemistry , total synthesis , stereochemistry , moiety , metathesis , epimer , cancer cell lines , cytotoxic t cell , ring closing metathesis , kinetic resolution , chemical synthesis , convergent synthesis , combinatorial chemistry , cancer cell , enantioselective synthesis , cancer , organic chemistry , biochemistry , in vitro , medicine , catalysis , polymerization , polymer
An efficient and convergent synthesis of 5′‐hydroxyzearalenone and 5′β‐hydroxyzearalenone, 14‐membered β‐resorcylic acid lactone (RAL) natural products, has been achieved in a longest linear sequence of 19 steps, and a total of 29 steps, starting from commercially available 5‐hexen‐1‐ol and methyl 2‐(3,5‐dimethoxyphenyl)acetate. The key features of our synthesis include a Jacobsen hydrolytic kinetic resolution, a Mitsunobu esterification and (an E )‐selective ring‐closing metathesis (RCM). Our synthesis also highlights the utility of the acetal protecting group for the resorcylate moiety, and its compatibility with RCM reactions for the synthesis of 14‐membered RALs. The cytotoxic activity of both synthetic compounds was evaluated against seven human cancer cell lines. 5′‐Hydroxyzearalenone shows more potent cytotoxic activity against most of the cancer cell lines tested than its epimer, 5′β‐hydroxyzearalenone. Both compounds show significant cytotoxic activity against the C33A cervical cancer cell line, with IC 50 values of 21.33 ± 6.43 µ m and 16.00 ± 12.17 µ m , respectively.