Organolithium-mediated diversification of peptide thiazoles

[Reaction: see text] We report a one-step, racemization-free method for the diversification of peptide thiazoles via direct lithiation of the thiazole ring. The method is compatible with N-Boc, N-trityl, carboxylic ester, and carboxamide protecting groups and has been used to directly functionalize the thiazole ring of cyclopeptide natural products.     

Decarboxylation syntheses of transition metal organometallics,II.trans-carbonyl(polyhalogenophenyl)bis(triphenylphosphine)rhodium(I) compounds

Summary The rhodium(I) carboxylates,trans-RhO₂CR(CO)(PPh₃)₂ (R = C₆F₅, C₆Cl₅,p-HC₆F₄,m-HC₆F₄,o-HC₆F₄,p-McOC₆F₄, 4,5-H₂C₆F₃, 3,5-H₂C₆F₃, or 2,6-F₂C₆H₃, have been prepared by reaction of RhH(CO)(PPh₃)₃ with the appropriate polyhalogenobenzoic acids in ethanol and/or by reaction oftrans-RhCl(CO)(PPh₃)₂ with the appropriate thallous carboxylates in benzene. Decarboxylations with formation of polyhalogenoarylrhodium(I) compounds,trans-RhR(CO)(PPh₃)₂ (R = C₆F₅, C₆Cl₅,p-HC₆F₄,m-HC₆F₄,p-MeOC₆F₄, 4,5-H₂C₆F₃ or 3,5-H₂C₆F₃), have been achieved either by decomposition of the corresponding rhodium(I) carboxylates in pyridine or by reaction oftrans-RhCl(CO)(PPh₃)₂ and the thallous carboxylates in pyridine, but the derivatives R =o-HC₆F₄ or 2,6-F₂C₆H₃ could not be obtained by this method. The rate of decarboxylation decreased in the sequence R = C₆F₅ >p-MeOC₆F₄ >p-HC₆F₄ >m-HC₆F₄ > 4,5-H₂C₆F₃ > 3,5-H₂C₆F₃.Part 1, ref. 10.Preliminary communication, ref. 9.     

Strategies to enhance the enzymatic hydrolysis of pretreated softwood with high residual lignin content

Pretreatment of Douglas-fir by steam explosion produces a substrate containing approx 43% lignin. Two strategies were investigated for reducing the effect of this residual lignin on enzymatic hydrolysis of cellulose: mild alkali extraction and protein addition. Extraction with cold 1% NaOH reduced the lignin content by only approx 7%, but cellulose to glucose conversion was enhanced by about 30%. Before alkali extraction, addition of exogenous protein resulted in a significant improvement in cellulose hydrolysis, but this protein effect was substantially diminished after alkali treatment. Lignin appears to reduce cellulose hydrolysis by two distinct mechanisms: by forming a physical barrier that prevents enzyme access and by non-productively binding cellulolytic enzymes. Cold alkali appears to selectively remove a fraction of lignin from steam-exploded Douglas-fir with high affinity for protein. Corresponding data for mixed softwood pretreated by organosolv extraction indicates that the relative importance of the two mechanisms by which residual lignin affects hydrolysis is different according to the pre- and post-treatment method used.     

Preparation of (R)-11-hydroxyaporphine directly from (R)-10,11-dihydroxyaporphine ((R)-apomorphine)

A Regioselective synthesis of (R)-11-hydroxyaporphine 2 directly from (R)-10,11-dihydroxyaporphine ((R)-apomorphine, 1 ) is described for the first time. The isopropylidene ketal ring of 10,11-(isopropyl-idenyldioxy)aporphine 5 obtained by the isopropylidenation of apomorphine was regioselectively opened by ten equivalents of trimethylaluminum to give (R)-10-hydroxy-11-tert-butyloxyaporphine 6 . The free 10-hydioxyl position of 6 was triflated with N-pbenyltrifluoromethanesulfonimide and potassium carbonate under reflux to give (R)-10-[(trifluoromethyl)sulfonyloxy]-11-tert-butyloxyaporphine 7 . The reduced product, 11-tert-butyloxyaporphine 8 was prepared from 7 by a palladium-catalyzed hydrogenolysis. The ether cleavage of (R)-11-tert-butyloxyaporphine with 48% hydrobromic acid afforded the desired (R)-11-hydroxyaporphine 2 in good yield.     

Design and synthesis of an isopenicillin N synthase mimic

Towards the aim of creating a functional mimic of isopenicillin N synthase, a small molecule designed to coordinate around iron(II) and model the enzyme active site has been prepared in nine synthetic steps from 2,6-bis(hydroxymethyl)pyridine, (S)-(+)-mandelic acid and pivaldehyde. One aspartate, two histidines and a water ligand in the natural enzyme are replaced by an α-hydroxy acid, pyridine and aniline in the model compound. Additionally, a free thiol designed to simulate the enzyme substrate, δ-(l-α-aminoadipoyl)-l-cysteinyl-d-valine, is linked to the ligand by a three carbon chain. We postulate that in the presence of molecular oxygen, the complex formed between this synthetic ligand and iron(II) will display oxidative chemistry similar to that observed in the active site of isopenicillin N synthase.     

Addition of palladium and platinum tri-tert-butylphosphine groups to Re-Sn and Re-Ge bonds

The reaction of Re2(CO)8[mu-eta2-C(H)=C(H)Bu(n)](mu-H) with Ph3SnH at 68 degrees C yielded the new compound Re2(CO)8(mu-SnPh2)2 (10) which contains two SnPh2 ligands bridging two Re(CO)(4) groups, joined by an unusually long Re-Re bond. Fenske-Hall molecular orbital calculations indicate that the bonding in the Re2Sn2 cluster is dominated by strong Re-Sn interactions and that the Re-Re interactions are weak. The 119Sn M?ssbauer spectrum of 10 exhibits a doublet with an isomer shift (IS) of 1.674(12) mm s(-1) and a quadrupole splitting (QS) of 2.080(12) mm s(-1) at 90 K,characteristic of Sn(IV) in a SnA2B2 environment. The IS is temperature dependent, -1.99(14) x 10(-4) mm s(-1) K(-1); the QS is temperature independent. The temperature-dependent properties are consistent with the known Gol'danskii-Kariagin effect. The germanium compound Re2(CO)8(mu-GePh2)2 (11) was obtained from the reaction of Re2(CO)8[mu-eta2-C(H)=C(H)Bu(n)](mu-H) with Ph3GeH. Compound 11 has a structure similar to that of 10. The reaction of 10 with Pd(PBu(t)3)2 at 25 degrees C yielded the bis-Pd(PBu(t)3) adduct, Re2(CO)8(mu-SnPh2)2[Pd(PBu(t)3)]2 (12); it has two Pd(PBu(t)3) groups bridging two of the four Re-Sn bonds in 10. Fenske-Hall molecular orbital calculations show that the Pd(PBu(t)3) groups form three-center two-electron bonds with the neighboring rhenium and tin atoms. The mono- and bis-Pt(PBu(t)3) adducts, Re2(CO)8(mu-SnPh2(2)[Pt(PBu(t)3)] (13) and Re2(CO)8(mu-SnPh2)2[Pt(PBu(t)3)]2 (14), were formed when 10 was treated with Pt(PBu(t)3)2. A mono adduct of 11, Re2(CO)8(mu-GePh2)2[Pt(PBu(t)3)] (15), was obtained similarly from the reaction of 11 with Pt(PBu(t)3)2.     

The determination of134Cs,137Cs,210Pb,226Ra and228Ra concentrations in nearshore marine sediments and seawater

Multi-radionuclide analyses of coastal marine sediments and seawater can be of considerable value in defining rates and mechanisms of nearshore processes. A preliminary study of¹³⁴Cs,¹³⁷Cs,²¹⁰Pb,²²⁶Ra and²²⁸Ra in the Clyde Sea Area has been performed. A summary of the marine geochemistries of these species and a detailed account of methods involved in their routine analysis are described.     

Measurement of PCDDs, PCDFs, and non-ortho-PCBs by comprehensive two-dimensional gas chromatography-isotope dilution time-of-flight mass spectrometry (GC x GC-IDTOFMS)

Comprehensive two-dimensional gas chromatography with isotope-dilution time-of-flight mass spectrometry (GC × GC-IDTOFMS) was used to measure polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofuran (PCDF), and coplanar polychlorinated biphenyl (cPCB) concentrations in ash, sediment, vegetation, and fish samples. The GC × GC capability was achieved by using a quad jet, dual stage, thermal modulator. Zone compression of the GC peaks from modulation resulted in a significant increase of the signal intensity over classical GC-IDTOFMS. The GC × GC column set used an Rtx-Dioxin 2 phase as the first dimension (¹D) and an Rtx-500 as the second dimension (²D). The chromatographic separation of the 17 PCDD/Fs and the 4 cPCBs was attained in ¹D except for 2,3,7,8-TCDD and CB126 for which deconvoluted ion currents (DIC) were required to be reported separately. The Rtx-500 phase separated the bulk matrix interfering compounds from the target analytes in ²D. The instrumental limit of detection (iLODs) was 0.5 pg for 2,3,7,8-TCDD. The calibration curves showed good correlation coefficients for all the compounds investigated in the concentration range of 0.5–200 pg. GC × GC-IDTOFMS results compared favorably to those from conventional isotope-dilution one-dimensional gas chromatography-high resolution mass spectrometry (GC-IDHRMS). The comprehensive mass analysis of the TOFMS further permitted the identification of other contaminants of concern in the samples.