A stereoselective synthesis of all functionalized C2–C10 fragment 13 of the antitumor marine natural product clavulactone was accomplished, starting from the commercially available 3-methylglutaric acid anhydride. Desymmetrization of 3-methylglutaric acid anhydride with (S)-α-phenylethanamine was successfully employed as a key step to embed the isolated C8-methyl group with the correct absolute configuration (99% de). The C3–C4 cis-double bond was stereospecifically furnished by an RCM (ring-closing metathesis) approach. Fragment 13 contains all preset functionalities and will be a useful precursor for the convergent total synthesis of clavulactone.

Small, organic, fluorescent molecules with large Stokes shifts and long emission wavelengths are ideal dyes for various modern fluorescent imaging technologies such as FRET. In this study, we designed and synthesized a number of new fluorescent molecules on the basic structures of two pyrrolocoumarin skeletons where Fischer's indole synthesis and the Suzuki coupling successfully served as the efficient molecular editing protocols. The examination of the fluorescent properties and further structural optimization of these compounds afforded three new pyrrolocoumarin dyes with notably large Stokes shifts and satisfactory fluorescent properties. Among these, 30 showed a large Stokes shift (113 nm) and intense fluorescence (φ = 0.55, λ_em = 523 nm), and thus showed great potential in biological imaging studies. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A new series of anticancer annonaceous acetogenin mimetics were designed, synthesized, and evaluated based on our previously developed compound AA005, in which a variety of conformationally constrained fragments were introduced. Parallel syntheses of all new compounds were accomplished by replacement of the acyclic bis-ether functionality of AA005 with certain conformationally constrained fragments. Slight effects to the anticancer activity were exerted by altering stereochemistries in the middle modification region. Similar to AA005, most newly synthesized mimetics were found to exhibit potent activities against breast cancer cells, and showed satisfactory selectivities between cancerous and non-cancerous cells. An N,N′-dimethyl bis-amide compound 67 exhibits 30 times more potency against MDA-MB-468 cells than its parent molecule AA005. This study indicates that the introduction of appropriate conformational constraints is a useful optimizing tool for this class of anticancer agents. Successes in the bis-amide analogues of AA005 make this unique class of anticancer agents much simpler and more flexible for future further developments.