Catalyzed asymmetric diels-alder reaction of benzoquinone. Total synthesis of (-)-ibogamine

The Diels-Alder addition of diene 2 with benzoquinone catalyzed by (S)-BINOL-TiCl(2) produced cycloadduct 5 in >65% yield and 87% ee. The cycloadduct was transformed into (-)-ibogamine in nine steps (10% overall yield from benzoquinone). A model for the transition state leading to 5 is proposed.     

Toward Daisy Chain Polymers: "Wittig Exchange" of Stoppers in

Two ammonium ion/crown ether-based [2]rotaxane monomers-each incorporating (i) a dumbbell-shaped component, possessing an exchangeable benzylic triphenylphosphonium stopper, and (ii) a ring component, bearing an aldehyde function-undergo a sequence of Wittig reactions in which the surrogate triphenylphosphonium stopper is exchanged for a ring component either (i) in the same rotaxane molecule to give cyclic daisy chains by an intramolecular, chain-terminating reaction or (ii) in another rotaxane molecule to give acyclic daisy chains by an intermolecular chain-propagating reaction.     

Growth arrest-specific gene 6 expression in proliferating rabbit vascular smooth muscle cells in vitro and in vivo

Proliferation and migration of vascular smooth muscle cells (VSMCs) are involved in the processes of atherosclerosis and restenosis. The protein product of the growth arrest-specific gene 6 (Gas-6) has recently been identified as a ligand for the Axl/Rse/Mer tyrosine kinase receptor family, which may be involved in proliferation and migration of VSMCs. Here we show that Gas-6 gene expression is increased in proliferating VSMCs in tissue culture (2.5-fold increase by Northern blot) and following neointimal proliferation in a rabbit balloon-injury model (3-fold increase by Western blot). Neither platelet-derived growth factor (PDGF) nor thrombin stimulate the expression of Gas-6 in cultured VSMCs despite the ability of the PDGF, but not thrombin, to stimulate proliferation in growth-arrested cells. These data suggest a role for the Gas-6 regulatory system in VSMC proliferation, which may be a target for therapeutic interventions in the atherosclerotic process and restenosis after angioplasty.     

Enantiospecific synthesis of (-)-trachyspic acid

The enantiospecific synthesis of (-)-trachyspic acid () is presented. This has allowed for the assignment of the absolute configuration of natural (+)-trachyspic acid as 3S,4S,6S.     

Ammonia diffusion and proton shifts in the alkaline earth hexaammines

Ammonia diffusion and proton shifts in Ca(NH₃)₆, Sr(NH₃)₆, and Ba(NH₃)₆ have been studied by high-resolution proton magnetic resonance. Ammonia diffuses rapidly in these compounds above ≈ 100 K by a hopping mechanism. Proton shifts are negative and very small and are interpreted in the light of recent ab initio calculations on metal—ammonia complexes.     

Kinetics of the thiazolium ion-catalyzed benzoin condensation.

The formation of benzoin (Ph-CHOH-CO-Ph) from two molecules of benzaldehyde, catalyzed by 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide in methanol buffered with Et(3)N/Et(3)NH(+)Cl(-) has been studied. Initial-rate studies at various concentrations of PhCHO (0.1-1.7 M) showed that the reaction is close to being first order in PhCHO. Following the reaction in deuteriomethanol, (1)H NMR spectroscopy allowed rate constants for all three kinetically significant steps to be determined. These show that all three steps are partially rate-determining. A normal deuterium kinetic isotope effect for the overall reaction (k(H)/k(D) approximately 3.4) is observed using PhCDO, and a large inverse solvent isotope effect (k(D)/k(H) approximately 5.9) is observed using deuteriomethanol, consistent with the kinetic scheme presented here.     

Synthesis of putative uniflorine A

A diastereoselective synthesis of the putative structure of the natural product uniflorine A has been achieved by using the Petasis borono-Mannich reaction and ring-closing metathesis as key steps. The NMR data of the synthetic material did not match that reported for the natural product. The structure of the final synthetic product was unequivocally determined by single-crystal X-ray study of its pentaacetate derivative. Thus it was concluded that the proposed structure of uniflorine A is incorrect.     

Simultaneous quantitation of zidovudine and zidovudine monophosphate from plasma, amniotic fluid and tissues by micellar capillary electrophoresis

Zidovudine (AZT) therapy given during pregnancy has been shown to reduce the vertical transmission of the human immunodeficiency virus (HIV) from mother to fetus. In order to investigate the efficacy of AZT, it is important to know the concentration of its active phosphorylated metabolites. We have developed the first CE method for the simultaneous quantitation of AZT and zidovudine monophosphate (AZT-MP) from rat plasma, amniotic fluid and fetal tissues. Sample extractions were performed by protein precipitation using acetonitrile for the plasma and amniotic fluids, while in fetal tissues solid phase extraction using Waters Oasis HLB extraction cartridges was used. Recoveries ranged from 78 to 92% for AZT, AZT-MP and 3'-azidouridine (internal standard, AZDU), in the three matrices. The optimum separation conditions were achieved using a 40 mm sodium dodecylsulfate (SDS) in 50 mm phosphate buffer (pH 7) with a run voltage of 15 kV. The CE system consists of a 75 microm i.d., 50 cm effective length uncoated fused silica capillary. The method was validated over the range 0.5-100 microg/ml ( micro g/g for tissues). Intra-day precision (RSD) and accuracy (%error) for AZT ranged from 0.13 to 11 and 0.68 to 11.1%, respectively, while for AZT-MP it ranged from 2.05 to 11.1 and 4.22 to 11.7%. Inter-day precision and accuracy for AZT ranged from 3.82 to 11.2 and 3.14 to 9.01%, while for AZT-MP it ranged from 3.9 to 9.32 and 3.44 to 9.37%, respectively. We also report the enzymatic dephosphorylation of AZT-MP in the placental tissue of rats. This new enzymatic pathway provides increased understanding of the mechanism of anti-viral transport in the rat during pregnancy.     

Synthesis of nitroxide-functionalized phthalocyanines

A nitroxide-functionalized phthalonitrile and a diimino-isoindoline were prepared via Pd(0)-catalyzed cyanation from the corresponding dibromide and subsequent addition of ammonia, without interference from the radical moieties. The structures of these radicals were confirmed by single-crystal X-ray structure determinations. Metal-templated macrocyclization of these species under standard Linstead conditions or in 2-(dimethylamino)ethanol at reflux gave the corresponding metallated and free-base phthalocyanines, which were characterized using UV-vis, FTIR and EPR spectroscopy as well as mass spectrometry.