We report the first synthesis of norbornyl-bridged acene dimers (2 and 3) with well-defined and controlled spatial relationships between the acene chromophore subunits. We employ a modular 2-D strategy wherein the central module, common to all our compounds, is a norbornyl moiety. The acenes are attached to this module using the Diels–Alder reaction, which also forms one of the acene rings. Manipulation of the Diels–Alder adducts provides the desired geometrically defined bis-acenes. The modular nature of this synthesis affords flexibility and allows for the preparation of a variety of acene dimers, including functionalized tetracene dimers.

The reaction of tert-butyl esters with SOCl2 at room temperature provides acid chlorides in unpurified yields of 89% or greater. Benzyl, methyl, ethyl, and isopropyl esters are essentially unreactive under these conditions, allowing for the selective conversion of tert-butyl esters to acid chlorides in the presence of other esters.

The use of bulky Lewis acids, aluminum tris(2,6-diphenylphenoxide) (ATPH) and aluminum tris(2,6-di-2-naphthylphenoxide) (ATNP), in the doubly vinylogous aldol reaction between methyl-5-methyl-2-furoate and aldehydes or ketones is described. These reactions proceed smoothly and in high yields with both enolizable and non-enolizable substrates. This C–C bond-forming reaction enables a new bond construction for the synthesis of functionalized furans.

A number of structurally and electronically diverse N-vinyl nitrones have been synthesized by a two-step method. The sequence consists of condensation of an α-chloroaldehyde or an α-phenoxy- or α-acetoxy ketone with a substituted benzyl hydroxylamine to provide the corresponding nitrone. Treatment of these species with a base induces a 1,4-elimination to provide the desired N-vinyl nitrone in good to excellent yields.

The use of the intramolecular vinylogous aldol reaction for the preparation of an advanced intermediate for the synthesis of peloruside A is described. The reaction was applied to compound 19 and proceeds in high yield and good levels of diastereoselectivity. Application of the Achmatowicz reaction to this intermediate provided the corresponding pyranone, a late stage intermediate well positioned for conversion to the natural product.

The synthesis of the novel Lewis acid, aluminum tris(2,6-di-2-naphthylphenoxide) (ATNP), and its use in the vinylogous aldol reaction between methyl crotonate and enolizable aldehydes are described. ATNP is related to Yamamoto’s Lewis acid, aluminum tris(2,6-diphenylphenoxide) (ATPH), but the 2-naphthyl groups more effectively block the α-position of aldehydes, enabling the selective enolization of crotonate esters in the presence of enolizable aldehydes. Vinylogous aldol reactions then proceed smoothly and in high yields with a variety of substrates.

We have recently characterized sliding motility in Bacillus subtilis strains that lack functional flagella, and here describe the discovery of inhibitors of colony spreading in these strains as well as the aflagellate pathogen, Bacillus anthracis. Aflagellate B. subtilis strains were used to screen for new types of antibacterials that might inhibit colony spreading on semi-solid media. From a diverse set of organic structures, p-nitrophenylglycerol (NPG), an agent used primarily in clinical laboratories to control Proteus swarming, was found to inhibit colony spreading. The four stereoisomers of NPG were synthesized and tested, and only the 1R,2S-(1R-anti) and 1R,2R-(1R-syn) NPG isomers had significant activity in a quantitative colony-spreading assay. Twenty-six NPG analogs and related structures were synthesized and tested to identify more active inhibitors. p-Methylsulfonylphenylglycerol (p-SPG), but not its ortho or meta analogs, was found to be the most effective of these compounds, and synthesis and testing of all four p-SPG stereoisomers showed that the 1R-anti-isomer was the most active with an average IC50 of 16 μM (3–5 μg mL−1). For B. anthracis, the colony-spreading IC50 values for 1R-anti-SPG and 1R-anti-NPG are 12 μM (2–4 μg mL−1) and >150 μM, respectively. For both Bacillus species tested, 1R-anti-SPG inhibits colony spreading of surface cultures on agar plates, but is not bacteriostatic or bacteriocidal in liquid cultures. Work is in progress to find the cellular target(s) of the NPG/SPG class of compounds, since this could lead to an understanding of the mechanism(s) of colony spreading as well as design and development of more potent inhibitors for the control of B. anthracis surface cultures.Percent inhibition of colony spreading of a Bacillus subtilis hag mutant (DS1677) at 15 μg mL−1.

The concise total synthesis of dermostatin A is described. Highlights include a two-directional application of the asymmetric acetate aldol method developed in our lab, a novel diastereotopic-group-selective acetal isomerization for terminus differentiation, and a selective cross-metathesis reaction between a terminal olefin and a trienal. A study of the scope and viability of similar cross-metathesis reactions is also described. The synthesis is convergent and utilizes fragments of roughly equal complexity.

A versatile method for the synthesis of 3,3-diaryloxindoles via Pd-catalyzed α-arylations or an SNAr reaction is described. The reaction proceeds using mild base, is tolerant of a variety of functional groups, and is capable of preparing hindered all-carbon quaternary centers.

The selective alkyl lithium-induced ring opening of 1,3-di-isopropylsilylenes is described. The reaction affords a differentially substituted 1,3-diol bearing a silane that resides at the oxygen in the more sterically demanding position. The reaction can be highly selective with a regiochemical preference up to >50:1 and likely proceeds via an alkoxy-silane intermediate. This intermediate can by trapped by methyl iodide to provide the corresponding silyl methyl ether, wherein the silane again resides at the oxygen in the more sterically demanding position.