Concise total Synthesis of Tropoloisoquinolines and Process Development of Bio-based Adipic Acid from Galactose

Abstract

This thesis comprises two chapters. Chapter 1 describes the concise total synthesis of tropoloisoquinolines via radical anionic coupling. Chapter 2 describes the process development of bio-based adipic acid from galactose by utilizing deoxydehydration process to remove oxygen contents.

Chapter 1. Tropoloisoquinoline alkaloids isolated from a plant family, Menispermaceae, which exhibit significant cytotoxic activity against leukemia P388 cell line. Motivated by its high cytotoxicity and unique structure, more concise and divergent syntheses of tropoloisoquinolines were accomplished by using commercially available bromoisoquinolines, based on previously established synthetic strategy employing radical anionic coupling of phenolic nitronate. The key intermediate, phenolic nitronate, was prepared by palladium-catalyzed coupling reaction between phenols and isoquinolines and following Reissert-type nitromethylgroup addition. As a result, various tropoloisoquinoline alkaloids including pareitropone have been synthesized

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and these compounds should be useful for structure-activity relationship (SAR) study. In the analogs, the number of the methoxy groups has been controlled from 0 to 3 and tropone moiety modified to chlorinated tropone. In particular, chlorinated tropone could be used for further functionalization on the tropone moiety. Chapter 2. Adipic acid, one of the commercially important dicarboxylic acids, was efficiently prepared from galactaric acid via deoxydehydration (DODH) process. DODH reaction was applied to remove two pairs of vicinal diols in galactaric acid, with the use of oxo-rhenium catalyst affording corresponding a key intermediate, muconate, First, an efficient large scale one-pot process was established for the mass production on bio-based adipic acid. The desired bio-based adipic acid was achieved in one-pot process that is consists of 4-step reaction: 1) esterification, 2) rhenium-catalyzed DODH reaction, 3) palladium-catalyzed hydrogenation, 4) hydrolysis. With our facile and green synthetic one-pot process, adipic acid was obtained at overall yield of 64% in high purity in 18 g scale from galactaric acid. Second, recyclable green process for bio-based adipic acid was developed by using ionic liquid as a reaction media. Relatively rare and expensive rhenium catalyst was recycled dissolved in ionic liquid. With ionic liquid-mediated DODH reaction, bio-based adipic acid was synthesized in quantitative yield, and the recovered ionic liquid was reused more than 10 times, affording the desired key intermediate muconate with similar yields.