The biosynthesis, structure and function of neuromelanin (NM), the dark brown melanin-like pigment present in the substantia nigra (SN), are not well characterized 1 , in spite of the possible involvement of NM in the etiology and pathogenesis of Parkinson's disease. NM was isolated from the SN of five non-Parkinsonian human brains. NM and synthetic melanins, employed as models, were characterized by chemical analysis. Alkaline hydrogen peroxide (H 2 O 2 ) oxidation of NM generated four degradation products, pyrrole-2,3-dicarboxylic acid (PDCA), pyrrole-2,3,5-tricarboxylic acid (PTCA), thiazole-4,5-dicarboxylic acid (TDCA) and thiazole-2,3,5-tricarboxylic acid (TTCA), whose ratios, especially the TTCA to PDCA ratio, indicate that NM is derived mostly from dopamine (DA) with 25% incorporation of cysteine (Cys) in the form of a benzothiazine structure. Hydriodic acid 2 (HI) reductive hydrolysis of NM yielded 4-amino-3-hydroxyphenylethylamine (4-AHPEA) as a marker of cysteinyldopamine (CysDA)-derived units. The 4-AHPEA to PDCA ratio indicates a 21% incorporation of CysDA-derived units into NM. These degradative experiments also suggest that DOPA is not incorporated into NM to a significant extent (approximately 6% the level of DA). It is concluded that the TTCA to PDCA ratio is a useful indicator of CysDA-derived units in NM, and NM consists mainly of DA-melanin with some contribution from Cys-DA-melanin. The involvement of DA and CysDA as building blocks of NM demonstrates the detoxifying role of NM synthesis, since it prevents the intraneuronal accumulation of DA and CysDA, which would cause toxic effects.

A new methodology for aromatic difluoromethylation is described. Aryl iodides reacted with α-silyldifluoroacetates upon treatment with copper catalyst in DMSO or DME to give the corresponding aryldifluoroacetates in moderate to good yields. The subsequent hydrolysis of aryldifluoroacetates and KF-promoted decarboxylation afforded a variety of difluoromethyl aromatics.

Starting from a readily available fluoral derivative, catalytic aromatic trifluoromethylation has been successfully achieved. A small amount of copper(I) iodide-phenanthroline complex catalyzed the cross-coupling reactions of aryl/heteroaryl iodides with the O-silylated hemiaminal of fluoral (trifluoroacetaldehyde) to provide trifluoromethylated arenes in moderate to high yields.

The structural motifs of trifluoromethylated aromatics (Ar‐CF3) have been widely employed in various industrial fields. The high lipophilicity, strong electron‐withdrawing ability, and characteristic size of the trifluoromethyl group is a key influence in the design of pharmaceuticals, agrochemicals, dyes, liquid crystals, and polymers. Therefore, a great deal of attention has been paid to convenient protocols of introducing trifluoromethyl groups into aromatic rings. With respect to the high regiochemical fidelity in aromatic substitution, the cross‐coupling of aryl halides with CF3Cu is one of the most powerful and versatile methods to construct trifluoromethylated aromatics.

The authors developed an HPLC assay for determining blood sirolimus concentration using a relatively simple solid-phase extraction and UV detection. The retention times of sirolimus and the internal standard, 32-desmethoxyrapamycin, are 8.7 and 9.3 minutes, respectively. The assay possesses linearity up to 200 ng/mL, sensitivity to 2.0 ng/mL, and day-to-day reproducibility of 8.8, 9.8, 6.1, and 6.4% at sirolimus concentrations of 6, 10, 20, and 30 ng/mL, respectively. A patient correlation study using this HPLC method and an established LC/MS/MS assay revealed a slope of 0.982 and intercept of -0.021 ng/mL and a correlation coefficient of 0.99 (n = 37). Of the 31 different drugs tested none interfered with the measurement of the drug of interest, and a recovery study gave an overall mean recovery of 101.8%. The authors conclude that the method described here is suited for the therapeutic monitoring of blood sirolimus concentration.

A convenient route to difluoromethylated pyridines was developed that involves copper-promoted cross-coupling of halopyridines with ethyl difluoro(trimethylsilyl)acetate and subsequent decarboxylation.

A short route to the required title compounds of type (IV) proceeds via coupling of halogenated pyridine systems with ester (I) followed by hydrolysis and decarboxylation.

A wide range of aryl iodides is coupled with silanes (I) or (IV) in the presence of CuI. Hydrolysis of the ester function according to A) followed by decarboxylation in the presence of KF or CsF produces the difluoromethyl analogues. Only in the case of (IIIg) no reaction takes place. -(FUJIKAWA, K.; FUJIOKA, Y.; KOBAYASHI, A.; AMII*, H.; Org. Lett. 13 (2011) 20, 5560-5563, http://dx.doi.org/10.1021/ol202289z ; Dep. Chem., Grad. Sch. Sci., Kobe Univ., Nada, Kobe 657, Japan; Eng.) -H. Simon 06-055