Concise total synthesis of the thiazolyl peptide antibiotic GE2270 A

The potent antibiotic thiazolylpeptide GE2270 A was synthesized starting from N-tert-butyloxycarbonyl protected valine in a longest linear sequence of 20 steps and with an overall yield of 4.8 %. Key strategy was the assembly of the 2,3,6-trisubstituted pyridine core by consecutive cross-coupling reactions starting from 2,6-dibromo-3-iodopyridine. The complete Southern fragment was installed by Negishi cross-coupling of 3-zincated 2,6-dibromopyridine at the terminal 2-iodothiazole of a trithiazole (87 %). The substituent at C-6 representing the Northern part of the molecule was introduced in form of the truncated tert-butyl 2-bromothiazole-4-carboxylate after metalation to a zinc reagent by another Negishi cross-coupling (48 %). Decisive step of the whole sequence was the macrocyclization to a 29-membered macrolactam, which was conducted as an intramolecular Stille cross-coupling occurring at C-2 of the pyridine core and providing the desired product in 75 % yield. The required stannane was obtained by amide bond formation (87 %) between a complex dithiazole fragment representing the Eastern part of GE2270 A and a 3,6-disubstituted 2-bromopyridine. Final steps included attachment of a serine-proline amide dipeptide to the Northern part of the molecule (65 %), formation of the oxazoline ring and silyl ether deprotection (55 % overall).     

Furanoside phosphite-phosphoroamidite: new ligand class for the asymmetric nickel-catalyzed trialkylaluminium addition to aldehydes

We have described the first successful application of bidentate ligands in the asymmetric Ni-catalyzed trialkylaluminium addition to several aldehydes. The ligands are prepared from inexpensive d-(+)-xylose and d-(+)-glucose and have the advantage of carbohydrate and phosphite/phosphoroamidite moieties. After systematic variation of the position of the phosphoroamidite group at either C5 or C-3, the configuration of C-3 and the substituents in the biaryl phosphite/phosphoroamidite moieties, enantioselectivities up to 84% and high yields were obtained in the Ni-catalyzed trialkylaluminium addition to several aldehydes.     

Amine-directed intramolecular hydroacylation of alkenes and alkynes

Medium-ring heterocycles are prepared via an amine-directed, rhodium(I)-catalyzed intramolecular hydroacylation. The presence of an allyl substituent on the amine accelerates the reaction and increases product yields.     

Assessment of amination reactions via nucleophilic aromatic substitution using conventional and eco-friendly energies

The efficiency of conventional heating energy source compared with Infrared (IR), Ultrasound (US), Microwave and the simultaneous combination US–IR eco-friendly approaches for preparation of new N-(5-R¹ _-amino-2-nitrophenyl)acetamides and 5-R¹-amino-2-nitroaniline by Nucleophilic Aromatic Substitution (S_NAr) via addition–elimination reactions on the halogens F, Cl, Br, I, employing amines as nucleophiles were explored. Moreover, phenyldiazenyl derivatives in good yields by an oxidative one-pot S_NAr-based amination reaction from an unusual oxidation of 2-phenylhydrazinyl derivatives in DMSO was prepared.     

Synthesis and characterization of stereoregular AABB‐type polymannaramides

The condensation of D ‐mannaro‐1,4:6,3‐dilactone ( 2 ) with even‐numbered alkylenediamines (C₂, C₆–C₁₂) in a methanol solution and in the presence of triethylamine afforded polymannaramides 3 – 7 , which were isolated directly as white solids with various hydrophobic–hydrophilic characters. Because all the stereocenters in 2 possessed an S configuration, the random polymerization led to optically active, stereoregular polyhydroxypolyamides. The polymers were characterized by elemental analysis and IR, ¹H NMR, and ¹³C NMR spectroscopy. Their number‐average molecular weights were estimated by ¹H NMR spectral integration analysis. Thermal and powder X‐ray diffraction studies revealed that compounds 3 – 7 were poorly crystalline. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1024–1030, 2001     

Inhibition of sulfur incorporation to transfer RNA by ultraviolet-A radiation in Escherichia coli

tRNA sulfurtransferase activity was assayed in Escherichia coli cell extracts obtained from bacterial suspensions exposed to a sub-lethal dose of ultraviolet-A radiation (fluence 148 kJ m(-2)) imparted at a low fluence rate (41 W m(-2)). We found that the irradiation reduced the enzymatic activity to one fourth of the control value, indicating that ultraviolet-A exposure inhibits the synthesis of 4-thiouridine, the most abundant thionucleoside in E. coli tRNA. Changes in the tRNA content of 4-thiouridine and its derived photoproduct 5-(4'-pyrimidin 2'-one) cytosine were studied in bacteria growing under ultraviolet-A irradiation. In these conditions the accumulation of photoproduct was limited, and the kinetics of this process was non-coincident with disappearance of 4-thiouridine. The results, which are compatible with the fact that ultraviolet-A induces an inhibition of the 4-thiouridine synthesis, suggest that the effect of radiation on tRNA modification is relevant to tRNA photo-inactivation in growing bacteria.     

Synthesis of two new thioesters bearing ferrocene: Vibrational characterization and ab initio calculations. X-ray crystal structure of S-(2-methoxyphenyl)ferrocenecarbothioate

Structural and conformational properties of S-benzyl ferrocenecarbothioate (I) and S-(2-methoxyphenyl) ferrocenecarbothioate (II) are analyzed using data obtained from X-ray diffraction, vibrational data and theoretical calculations. According to chemical quantum calculations, the synperiplanar and antiperiplanar forms are found as the first and second more stable conformations, respectively, for the title compounds. The geometric parameters and normal modes of vibration were calculated using a density functional theory method (B3LYP) and the 6-31+G∗∗ basis set for all atoms except for iron. For this atom the calculations were carried out with the Lanl2dz basis set. The calculated parameters are in good agreement with the corresponding X-ray diffraction values. The combined experimental and theoretical approach allows a consistent assignment for most of the fundamental modes.     

Transient reduction in the tRNA 4-thiouridine content induced by ultraviolet A during post-irradiation growth in Enterobacter cloacae

The influence of previous exposure to ultraviolet-A radiation (UVA) was studied on the susceptibility of Enterobacter cloacae to undergo the growth delay effect. Comparison of growth curves corresponding to irradiated and control cells showed that a previous treatment with UVA almost abolished the growth delay effect. UV absorption spectra of tRNA, and reverse phase HPLC analysis of hydrolysed tRNA, demonstrated a low content of 4-thiouridine in E. cloacae cells grown after UVA exposure at low doses. Since 4-thiouridine is the UVA target responsible for initiation of growth delay, this observation explained the influence of previous exposure to UVA on the susceptibility of this organism to undergo growth delay. A similar but weaker alteration was found when Escherichia coli was assayed. The results suggest that, in addition to cross-linking with cytidine residues, the content of 4-thiouridine in tRNA may be modified by UVA by an unknown mechanism.