%0 Journal Article
%T Synthetic Studies on Potent Marine Drugs: Synthesis and the Crystal Structure of 6-tert-butyl-4-phenyl-4H-chromene-2-carboxylic Acid
%A Hui-Jing Li
%A Jun-Li Wang
%A Rui Wang
%A Dong-Hui Luo
%A Yan-Chao Wu
%J Journal of Chemistry
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/106908
%X 4H-Chromene-2-carboxylic acid ester derivatives of renieramycin M might be of use for the structural-activity relationship studies of antitumor antibiotic tetrahydroisoquinoline natural products. Accordingly, 6-tert-butyl-4-phenyl-4H-chromene-2-carboxylic acid, one key intermediate, was synthesized via the condensation of (3E)-2-oxo-4-phenylbut-3-enoate methyl ester with 4-tert-butylphenol in the presence of AuCl3/3AgOTf (5£¿mol%), followed by cyclodehydration and aqueous hydrolysis. The product was unambiguously shown to the 4H-chromene-2-carboxylic acid by spectroscopy and X-ray crystallographic analysis. A packing diagram of the crystal structure shows that aromatic -stacking interactions and O¨CH£¿O hydrogen bond stabilize the structure in the solid. 1. Introduction Antitumor antibiotic renieramycin M (5, Figure 1) has been isolated from the marine sponge Xestospongia sp. in 2003 [1¨C3], which belongs to a family of tetrahydroisoquinoline natural products including ecteinascidin 743 (1, Et-743, yondelis, trabectedin), saframycin A (3), quinocarcin, and so forth [4¨C20]. These natural products show potent antitumor antibiotic activities, and Et-743 has received European approval for the treatment of soft tissue sarcoma and ovarian carcinoma [21]. The remarkable clinical results of Et-743 have stimulated the discovery of zalypsis (2) that is currently in advanced human clinical trials for treating Ewing¡¯s sarcoma [22, 23]. It is noteworthy that quinoline-2-carboxylic acid amide derivative of saframycin A (QAD, 4) was shown to possess single-digit picomolar potency against three human sarcoma cell lines 100 times more potent than Et-743 [24]. On the other hand, the ester side chain structure of renieramycin M was also found to have a critical impact on its antitumor activities [25]. We envisioned that 4H-chromene-2-carboxylic acid ester derivatives of renieramycin M (6) might be of some use for the structural-activity relationship studies of this antitumor antibiotic marine natural product. Compound 6 was thought to be prepared from pentacyclic alcohol 7 by the selective acylation of the primary alcohol with 4H-chromene-2-carboxylic acids (8, Scheme 1). We have already reported the synthesis of compound 7 in our asymmetric total synthesis of renieramycin M and jorumycin [9]. Herein, we would like to report our endeavors on the synthesis of 4-phenyl-4H-chromene-2-carboxylic acid 8a. As the structure of this product might be possible 4-phenyl-2H-chromene-2-carboxylic acid 9a or 2-phenyl-2H-chromene-4-carboxylic acid 10a, X-ray crystallographic analysis was
%U http://www.hindawi.com/journals/jchem/2013/106908/