Design of pure heterodinuclear lanthanoid cryptate complexes

Heterolanthanide complexes are difficult to synthesize owing to the similar chemistry of the lanthanide ions. Consequently, very few purely heterolanthanide complexes have been synthesized. This is despite the fact that such complexes hold interesting optical and magnetic properties. To fine-tune these properties, it is important that one can choose complexes with any given combination of lanthanides. Herein we report a synthetic procedure which yields pure heterodinuclear lanthanide cryptates LnLn*LX(3) (X = NO(3)(−) or OTf(−)) based on the cryptand H(3)L = N[(CH(2))(2)N[double bond, length as m-dash]CH–R–CH[double bond, length as m-dash]N–(CH(2))(2)](3)N (R = m-C(6)H(2)OH-2-Me-5). In the synthesis the choice of counter ion and solvent proves crucial in controlling the Ln–Ln* composition. Choosing the optimal solvent and counter ion afford pure heterodinuclear complexes with any given combination of Gd(iii)–Lu(iii) including Y(iii). To demonstrate the versatility of the synthesis all dinuclear combinations of Y(iii), Gd(iii), Yb(iii) and Lu(iii) were synthesized resulting in 10 novel complexes of the form LnLn*L(OTf)(3) with LnLn* = YbGd 1, YbY 2, YbLu 3, YbYb 4, LuGd 5, LuY 6, LuLu 7, YGd 8, YY 9 and GdGd 10. Through the use of (1)H, (13)C NMR and mass spectrometry the heterodinuclear nature of YbGd, YbY, YbLu, LuGd, LuY and YGd was confirmed. Crystal structures of LnLn*L(NO(3))(3) reveal short Ln–Ln distances of ∼3.5 Å. Using SQUID magnetometry the exchange coupling between the lanthanide ions was found to be anti-ferromagnetic for GdGd and YbYb while ferromagnetic for YbGd

An Improved Process for the Preparation of Highly Pure Solifenacin Succinate via Resolution through Diastereomeric Crystallisation

An improved process for the preparation of solifenacin succinate (<b>1</b>) involving resolution through diastereomeric crystallization is described. (1<i>S</i>)-IQL derivative (<b>5</b>) is esterified to form (1<i>S</i>)-ethoxycarbonyl IQL derivative (<b>6</b>) which is condensed with (<i>RS</i>)-3-quinuclidinol (<b>7</b>) to form a solifenacin diastereomeric mixture (<b>8</b>); this is subjected to resolution through diastereomeric crystallization to produce solifenacin succinate (<b>1</b>), which is used for the treatment of an overactive bladder

Bringing biocatalytic deuteration into the toolbox of asymmetric isotopic labelling techniques

Enzymes dependent on nicotinamide cofactors are important components of the expanding range of asymmetric synthetic techniques. New challenges in asymmetric catalysis are arising in the field of deuterium labelling, where compounds bearing deuterium (2H) atoms at chiral centres are becoming increasingly desirable targets for pharmaceutical and analytical chemists. However, utilisation of NADH-dependent enzymes for 2H-labelling is not straightforward, owing to difficulties in supplying a suitably isotopically-labelled cofactor ([4-2H]-NADH). Here we report on a strategy that combines a clean reductant (H2) with a cheap source of 2H-atoms (2H2O) to generate and recycle [4-2H]-NADH. By coupling [4-2H]-NADH-recycling to an array of C=O, C=N, and C=C bond reductases, we demonstrate asymmetric deuteration across a range of organic molecules under ambient conditions with near-perfect chemo-, stereo- and isotopic selectivity. We demonstrate the synthetic utility of the system by applying it in the isolation of the heavy drug (1S,3'R)-[2',2',3'-2H3]-solifenacin fumarate on a preparative scale