A Synthetic Approach to Bengazoles: A Synthesis of Deacylbengazole

The synthesis of deacylbengazole (3) and the C1-C9 fragments (4 and 5) of bengazoles was accomplished by use of the Thomas SnCl 4 -assisted coupling of the oxazole aldehydes with δ-alkoxyallylstannanes followed by the Sharpless asymmetric dihydroxylation as key steps.Bengazoles are a group of bisoxazole containing marine natural products with a carbohydrate-like polyol side chain, 1 and bengazoles A (1) and B were first isolated from Jaspis sponge by Crews and co-workers in 1988.1a Subsequently, bengazole A and their homologues were isolated by Molinski and co-workers who determined their complete absolute configuration to be 1 based on NMR and chiroptical studies.1e Bengazoles so far isolated will be classified into two groups: one contains the bis(oxazolyl)methanol as represented by bengazole A (1) and the other has no hydroxy function at C10 like bengazole Z (2).1c,1f Intriguing biological activities such as anthelminthic, cytotoxic, and ergosterol dependent antifungal activities together with the unique bisoxazole array having the polyol side chain have attracted us to devise a novel approach to their synts asn ha an extension of our synthetic efforts on biologically active aquatic natural products. 2Molinski and co-workers already reported 3a,b the synthesis of the advanced C1-C9 fragment utilizing the ambident nucleophilicity of 2-lithiooxazoles to couple with a D-galactose derivative, a side chain equivalent, and they succeeded in the total synthesis of bengazole A (1) though asMeSO 2 NH 2 , Bu t OH-H 2 O (1:1), 2 days, 0 C, 85% (2 steps), syn / anti = 6 / 7. c) H 2 , 10% Pd/C, EtOH, rt, 12 h, quantitative.d) Me 3 SiBr, CH 2 Cl 2, 0 °C, 2 h, 95 %.