Elvia V. Cabrera, Ari Gil, J. Ortega
May 4, 2014
Citations
0
Influential Citations
3
Citations
Journal
Organic Preparations and Procedures International
Abstract
6-Isopropropyl-7-methoxy-1-tetralone1 (2) and 6-isopropyl-7-methoxy-2-tetralone2 (4) have been claimed to be potential intermediates for the synthesis of natural products related to diterpenes miltirone (5) and carnosic acid (6), respectively. Miltirone, a tanshinone (ortho-quinone diterpene), isolated from S. miltiorrhiza3 and other species,4 has previously been synthesized5,6 and is cytotoxic against a number of cultured tumor cell lines.7 Carnosic acid, a naturally occurring catechol-type polyphenolic diterpene, is obtained8 from Rosmarinus officinalis (rosemary) leaves and has also been synthesized previously.9,10 Carnosic acid is known to possess potent anti-oxidant activity as well as anti-cancer and anti-viral properties.11–13 In 1990, a four-step synthesis of tetralone 2 from 2-isopropylphenol in an overall yield of 24% was reported1 and the preparation of tetralone 4 from 2,7-dimethoxynaphthalene was accomplished in six steps with an overall yield of 39%.2 A concise and high-yield approach to tetralones 2 and 4 would be useful for the scaleup preparation of the previously mentioned and related natural products. In addition, the synthesis of these two tetralones in high yields would be advantageous for pre-clinical and clinical evaluations of 5 and 6. Our experience in the studies on the synthesis of α,βsubstituted tetralones14,15 encouraged us to develop a concise approach for the tetralones 2 and 4. The present article describes for the first time a short approach for the tetralones 2 and 4 in high yields. To a mixture of polyphosphoric acid (PPA) and isopropanol (i-PriOH) previously heated to 75◦C–80◦C, was added commercially available 7-methoxy-1-tetralone (1) and