Enantio- and Diastereoselective Synthesis of Chiral Allenes by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition Reactions.

A protocol for the asymmetric synthesis of highly substituted chiral allenes with control of point and axial chirality has been developed. A palladium-catalyzed [3+2] cycloaddition using readily available racemic allenes gives access to densely functionalized chiral allenes with excellent yields and functional group tolerance. The catalytic asymmetric protocol utilizes a broad range of allenyl TMM (trimethylenemethane) donors to form cyclopentanes, pyrrolidines, and spirocycles with very good control of regio-, enantio-, and diastereoselectivity. The chiral allene moiety is shown to be a valuable functional group for rapid elaboration towards complex targets.

Asymmetric synthesis of diamine derivatives via sequential palladium and rhodium catalysis.

The use of a bifunctional nitrogen nucleophile and an allyl carbonate starting material in successive enantioselective palladium- and diastereoselective rhodium-catalyzed reactions enables the rapid assembly of unique amino aziridine products. Further elaboration of these materials affords complex, stereodefined polyamine architectures, thus demonstrating the power of these combined methods for simplifying asymmetric C-N bond construction.

KLF4 is a FOXO target gene that suppresses B cell proliferation.

Lymphocytes circulate in a quiescent (G(0)) state until they encounter specific antigens. In T cells, quiescence is programmed by transcription factors of the forkhead box O (FOXO) and Krüppel-like factor (KLF) families. However, the transcription factors that regulate B cell quiescence are not known. KLF4 is a candidate tumor suppressor gene in B lymphocytes, and thus a likely candidate for regulating B cell homeostasis. Here, we show that RNA and protein expression of murine KLF4 decreases following B cell activation. Forced expression of KLF4 in proliferating B cell blasts causes a G(1) cell cycle arrest. This effect requires the DNA binding and transactivation domains of KLF4 and correlates with changes in the expression of known KLF target genes. We present evidence that Klf4 is a target gene for FOXO transcription factors, which also suppress B cell proliferation. To determine the effect of KLF4 loss-of-function, we generated mice with B cell-specific deletion of the Klf4 gene. These mice exhibited normal B cell development and function with no evidence of a lowered activation threshold. Collectively, our findings indicate that KLF4 has growth-suppressive properties in B cells but might be redundant with other members of the KLF family in maintaining B cell quiescence.

Disposable microfluidic sensor arrays for discrimination of antioxidants.

A microfluidic colorimetric sensor array was developed for detection and identification of various antioxidants. The sensor was fabricated by a photolithographic method, and consists of an array of printed cross-responsive indicators. The microfluidic design also incorporates pre-activation spots to allow printing of chemically incompatible components separately. Separately printed oxidizer allowed an oxidation of adjacent redox indicators only when aqueous sample was added to the sensor cartridge. Antioxidants were primarily detected by measuring the extent of inhibition of this oxidation reaction. Using this flow-based technique, a clear differentiation of 8 different antioxidants and 4 different teas has been demonstrated with 98.5% sensitivity.

Synthesis and reactivity of unique heterocyclic structures en route to substituted diamines.

Rhodium-catalyzed oxidative cyclization of allylic hydroxylamine-derived sulfamate esters furnishes a novel family of bicyclic aziridines that serve as functional precursors to substituted diamines. Investigations with the N4-Troc form of these heterocycles have led to manifold improvements in reaction performance and scope and have revealed unique differences in the stability and reactivity of such compounds dictated by the choice of N4-protecting group.