Synthesis of resveratrol using a direct decarbonylative Heck approach from resorcylic acid

The phytoalexin resveratrol has been made using a decarbonylative Heck reaction. The acid chloride derived from 3,5-dihydroxybenzoic acid was coupled with 4-acetoxystyrene in the presence of palladium acetate and N,N-bis-(2,6-diisopropylphenyl)dihydroimidazolium chloride to give the substituted stilbene in 73% yield as the key step.     

Iridium-catalyzed alternative of the Meinwald rearrangement

A novel and easy to handle procedure for the regioselective rearrangement of epoxides has been developed, based on an iridium catalyst.     

Determination of the strange quark content of the nucleon from a next-to-leading-order QCD analysis of neutrino charm production

We present the first next-to-leading-order QCD analysis of neutrino charm production, using a sample of 6090 ^– and -induced opposite-sign dimuon events observed in the CCFR detector at the Fermilab Tevatron. We find that the nucleon strange quark content is suppressed with respect to the non-strange sea quarks by a factor =0.477 _–0.053 ^+0.063 , where the error includes statistical, systematic and QCD scale uncertainties. In contrast to previous leading order analyses, we find that the strange seax-dependence is similar to that of the non-strange sea, and that the measured charm quark mass,m _c =1.70±0.19 GeV/c², is larger and consistent with that determined in other processes. Further analysis finds that the difference inx-distributions betweenxs(x) and is small. A measurement of the Cabibbo-Kobayashi-Maskawa matrix element |V _cd |=0.232 _–0.020 ^+0.018 is also presented.     

Coupling to the pyrimido[4,5-b][1,4]oxazine ring system: Synthesis of potential antifolates

The ability of 2-amino-4-hydroxy-7H-pyrimido[4,5-b][1,4]oxazine derivatives to inhibit dihydrofolate reductase led to a search for means of synthesizing new side chain substituted analogs of this marginally stable pyrimidooxazine system. A study of the synthesis and use of 6-functionalized pyrimido[4,5-b][1,4]oxazines for coupling side chains was begun and has now revealed methods for coupling p-aminobenzoic acid with 2-amino-4-hydroxy-6-carboxy-7H-pyrimido[4,5-b][1,4]oxazine and hydrolyzed 2-amino-4-hydroxy-6-carbe-thoxymethylene-6,7-dihdyro-5H-pyrimido[4,5-b][1,4]oxazine. The products are of interest for evaluation as potential antifolates.     

Highly enantioselective copper-bisoxazoline-catalyzed allylic oxidation of cyclic olefins with tert-butyl p-nitroperbenzoate

Catalytic asymmetric allylic oxidation of cyclic olefins ocurrs for the first time in very high (94-99% ee) enantioselectivity using copper(I) complexes of malonyl derived bisoxazolines and tert-butyl p-nitroperbenzoate giving allyl benzoates in moderate yield. The copper complex, 15 mol %, was used in acetonitrile at -20 degrees C over an extended period, 5-12 d, with excess olefin together with one equivalent of perester. The S-esters were generated in accord with the model proposed previously for the (S,S)-bisoxazoline ligand. An eta2 intermediate was ruled out using low-temperature 13C NMR with the complex in the presence of olefin.     

A study of wrong-sign single muon production inv μ-nucleon interaction

We report on a search forv _μ-induced events where the single emerging muon carries lepton number opposite that of the incident neutrino. The rate and kinematic quantities of the candidate events are compared with known backgrounds from \(\bar v_\mu \) -induced charged current interactions and ν-induced interactions that produce dileptons. We derive an upper limit on the rate of wrong-sign single muon production relative to the rate ofv _μ charged current interactions to be 1.6×10^?4 fory<0.5 and 3.1×10^?4 fory>0.5 (90% CL). These upper limits enable us to constrain exotic sources of wrong-sign muons such as the charm component of the nucleon sea, flavor changing neutral currents and lepton number violating processes. Finally, the rate and kinematic properties of these events are compared with those of the neutrino-induced opposite-sign dimuon events.     

Solution and crystallographic studies of branched multivalent ligands that inhibit the receptor-binding of cholera toxin

The structure-based design of multivalent ligands offers an attractive strategy toward high affinity protein inhibitors. The spatial arrangement of the receptor-binding sites of cholera toxin, the causative agent of the severe diarrheal disease cholera and a member of the AB(5) bacterial toxin family, provides the opportunity of designing branched multivalent ligands with 5-fold symmetry. Our modular synthesis enabled the construction of a family of complex ligands with five flexible arms each ending with a bivalent ligand. The largest of these ligands has a molecular weight of 10.6 kDa. These ligands are capable of simultaneously binding to two toxin B pentamer molecules with high affinity, thus blocking the receptor-binding process of cholera toxin. A more than million-fold improvement over the monovalent ligand in inhibitory power was achieved with the best branched decavalent ligand. This is better than the improvement observed earlier for the corresponding nonbranched pentavalent ligand. Dynamic light scattering studies demonstrate the formation of concentration-dependent unique 1:1 and 1:2 ligand/toxin complexes in solution with no sign of nonspecific aggregation. This is in complete agreement with a crystal structure of the branched multivalent ligand/toxin B pentamer complex solved at 1.45 A resolution that shows the specific 1:2 ligand/toxin complex formation in the solid state. These results reiterate the power of the structure-based design of multivalent protein ligands as a general strategy for achieving high affinity and potent inhibition.     

Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin: asymmetric glycolate aldol reactions and biological evaluation

The total synthesis of (+)-geldanamycin (GA), following a linear route, has been completed using a demethylative quinone-forming reaction as the last step. Key steps include the use of two new asymmetric boron glycolate aldol reactions. To set the anti-C11,12 hydroxymethoxy functionality, (S,S)-5,6-bis-4-methoxyphenyldioxanone 8 was used. Methylglycolate derived from norephedrine 5 set the C6,7 methoxyurethane stereochemistry. The quinone formation step using nitric acid gave the non-natural o-quino-GA product 55 10:1 over geldanamycin. Other known oxidants gave an unusual azaquinone product 49. o-Quino-GA 55 binds Hsp90 with good affinity but is less cytotoxic compared to GA.     

Immobilized Biomaterials—Techniques and Applications

The immobilization of enzymes, cofactors and whole cells offers the potential of economical exploitation of biomaterial activity. Enzymes or cells can be immobilized by binding to carriers through adsorption or covalent linkages or by entrapment in a polymer matrix or microencapsulation. The development of immobilized biomaterial systems requires the involvement of biochemical, kinetics and reactor design principles. Examples of commercial scale applications of immobilized biomaterial systems are the production of a fructose-rich syrup from starch and the synthesis of L -amino acids by selective hydrolysis of N-acyl-D ,L -amino acids.