Polyamidoamine (PAMAM) dendrimers represent one of the most efficient polymeric gene carriers. This study describes a new family of PAMAM dendrimers that can be synthesized using a Pentaerythritol derivative (PD) as a core that possesses 12 branches. This new approach in the synthesis of divergent dendrimers provided a rapid increase in the number of branches, which made it easier to obtain dendrimers with high generation and large enough molecular size. The PD dendrimers of generations 3-5 synthesized in this study could efficiently condense DNA into nanoscale complexes with slightly positive charges. Their transfection efficiency was evaluated in different cell lines. These PD dendrimers were found to show higher transfection efficiency, but much lower cytotoxicity, than the commercial nonviral gene carriers polyethyleneimine (PEI), polylysine (PLL), and PAMAM dendrimers with an ethylenediamine core (generations 5 and 7). The results indicate that, with high transfection efficiency and low cytotoxicity, the PD dendrimers hold promise as novel nonviral gene carriers.

Preparation and Physical Data of Racemic α-Arylaldehydes…………….. S2 (B) General Procedure for the Preparation of Catalysts 3……………………. S7 (C) General Procedure for Asymmetric Hydrogenation………………………. S8 (D) Synthesis of (S)-2-(4-Chlorophenyl)-3-methylbutanoic Acid (4)………. …S15 (E) Synthesis of BAY × 1005………………………………………………… ….S15 (F) Hydrogenation of Aldehyde 1c with D 2 ………………………………… ….S18 (G) NMR Spectra for New α-Arylaldehydes and Chiral Primary Alcohols ….S20 (H) GC or HPLC Chart for Hydrogenation Product and Other Compounds..S38 S2 General remarks. All reactions and manipulations were performed in an argon-filled glovebox (VAC DRI-LAB HE 493) or using standard Schlenk techniques. 1 H, 13 C and 31 P NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400

The highly efficient asymmetric hydrogenation of alpha-arylmethylene cycloalkanones catalyzed by Ir-complexes of chiral spiro aminophosphine ligands was developed, providing chiral exo-cyclic allylic alcohols at high yields with excellent enantioselectivities (up to 97% ee) and high turnover numbers (S/C up to 10,000). This new reaction provided an efficient method for the synthesis of the key intermediate of the active form of the anti-inflammatory loxoprofen.

A highly efficient asymmetric hydrogenation of racemic acyclic alpha-amino aliphatic ketones via dynamic kinetic resolution has been realized, providing chiral amino alcohols in excellent enantioselectivities and diastereoselectivities. A hydrogen-bonding transition state mode was proposed for explaining the high diastereoselectivity and enantioselectivity of the reaction.

L-type amino acid transporter 1 (LAT1), overexpressed on the membrane of various tumor cells, is a potential target for tumor-targeting therapy. This study aimed to develop a LAT1-mediated chemotherapeutic agent. We screened doxorubicin modified by seven different large neutral amino acids. The aspartate-modified doxorubicin (Asp-DOX) showed the highest affinity (Km = 41.423 μmol/L) to LAT1. Aspartate was attached to the N-terminal of DOX by the amide bond with a free carboxyl and a free amino group on the α-carbon atom of the Asp residue. The product Asp-DOX was characterized by HPLC/MS. In vitro, Asp-DOX exerted stronger inhibition on the cancer cells overexpressing LAT1 and the uptake of Asp-DOX was approximately 3.5-fold higher than that of DOX in HepG2 cells. Pharmacokinetic data also showed that Asp-DOX was expressed over a longer circulation time (t1/2 = 49.14 min) in the blood compared to DOX alone (t1/2 = 15.12 min). In HepG2 and HCT116 tumor-bearing mice, Asp-DOX achieved 3.1-fold and 6.4-fold accumulation of drugs in tumor tissue, respectively, than those of the unmodified DOX. More importantly, treatment of tumor-bearing mice with Asp-DOX showed a significantly stronger inhibition of tumor growth than mice treated with free DOX in HepG2 tumor models. Furthermore, after Asp modification, Asp-DOX avoided MDR mediated by P-glycoprotein. These results suggested that the Asp-DOX modified drug may provide a new treatment strategy for tumors that overexpress LAT1 and MDR1.