Concise Stereoselective Total Synthesis of Leiocarpin C

Introduction. – The styryl lactones have become a hot topic of phytochemistry and oncopharmacology after taxol. The genus Goniothalamus (Annonaceae) comprises a broad spectrum of styryl lactones, and its species were widely used as traditional medicines in China as antalgic and pesticide agents [1]. The extract of the seeds of Goniothalamus amuyon has been employed for the treatment of edema and rheumatism [2]. Other general applications include their use as painkillers and mosquito repellents. Taking into account their medicinal properties [3], these plants are considered a potential source of antitumor, antifungal, and antibiotic agents [4]. Leiocarpin C (1) is a natural styryl lactone, which was isolated from the stem bark of the tropical plant Goniothalamus leiocarpus [5]; it possesses significant cytotoxic activity against several human tumor cell lines [6]. The synthesis of styryl lactones is of considerable interest due to the prevalence of these structures in natural products as biologically active compounds. Our continued interest in the total synthesis of lactones [7] prompted us to undertake the synthesis of leiocarpin C (1). Three cumbersome syntheses were reported in the literature for the synthesis of 1 [8]. Herein, we report a simple synthesis of 1 using cis-dihydroxylation with OsO4 [7a] [9] and selective 1,3-antireduction with K-Selectride [10], starting from commercially available methyl (R)mandelate (1⁄4methyl (R)-2-hydroxy-2-phenylylacetate; 2).