OBJECTIVE -To evaluate perinatal outcome in pregnancies in women with type 1 and type 2 diabetes and the influence of preconception care 10 years after the St. Vincent's declaration.
RESEARCH DESIGN AND METHODS-A cross-sectional study was conducted in 12 perinatal centers in France in 2000 -2001. The main investigated outcomes were perinatal mortality, major congenital malformations, and preterm delivery.RESULTS -Among 435 single pregnancies, 289 (66.4%) were from women with type 1 and 146 (33.6%) from women with type 2 diabetes. Perinatal mortality rate was 4.4% (0.7% national rate), severe congenital malformations rate was 4.1% (2.2% national rate), and preterm delivery rate was 38.2% (4.7% national rate). Preconception care was provided in 48.5% women with type 1 diabetes and in 24.0% women with type 2 diabetes. Women whose first trimester HbA 1c was Ͼ8% had higher rates of perinatal mortality (9.2 vs. 2.5%; odds ratio 3.9; 95% CI 1.5-9.7; P Ͻ 0.005), major congenital malformations (8.3 vs. 2.5%; 3.5; 1.3-8.9; P Ͻ 0.01), and preterm delivery (57.6 vs. 24.8%; 1.4; 1.1-1.7; P Ͻ 0.005) than those with first trimester HbA 1c Ͻ8%. These results are similar to those reported in France in 1986 -1988.CONCLUSIONS -Pregnancies in women with diabetes are still poorly planned and complicated by higher rates of perinatal mortality and major congenital malformations. Despite knowledge of the importance of intensified glycemic control before pregnancy, reaching the St. Vincent's target needs further implementation in France.
Diabetes Care 26:2990 -2993, 2003I n 1989, representatives of the government health departments and patients' organizations from all of the European countries met with diabetes experts under the aegis of the Regional Offices of the World Health Organization and the International Diabetes Federation in St. Vincent, Italy, and identified goals to be achieved in the treatment of diabetes (1). One of the declared aims was that within 5 years, "pregnancy outcome of diabetic women should approximate that of the nondiabetic women." Previous studies have shown that such results may be obtained in women with type 1 diabetes by providing effective preconception care and intensive support to improve glycemic control before and during the whole pregnancy (2-5). However, this was achieved in selected populations and in specialized units. By contrast, several surveys done in nonselected, geographically based populations showed that the prognosis of pregnancy in women with type 1 diabetes remains poorer than that of the general population (6,7). Moreover, new issues have been raised by the increasing prevalence of type 2 diabetes in pregnancy (8). Particularly, type 2 diabetes often remains unrecognized, and the rate of perinatal mortality in women with type 2 diabetes may be higher than in those with type 1 diabetes (9).In 1986 -1988, a multicenter survey of pregnancies in women with diabetes was performed in France (10). It essentially showed that the rate of perinatal mortality was 1.9% in women with type 1 diabete...
The stereochemical role of the phosphoramidite ligand in the asymmetric conjugate addition of alkylzirconium species to cyclic enones has been established through experimental and computational studies. Systematic, synthetic variation of the modular ligand established that the configuration of the binaphthol backbone is responsible for absolute stereocontrol, whereas modulation of the amido substituents leads to dramatic variations in the level of asymmetric induction. Chiral amido substituents are not required for enantioselectivity, leading to the discovery of a new family of easily synthesized phosphoramidites based on achiral amines that deliver equal levels of selectivity to Feringa's ligand. A linear correlation between the length of the aromatic amido groups and experimentally determined enantioselectivity was uncovered for this class of ligand, which, following an optimisation, leading to the highly selective ligands (up to 94% ee) with naphthyl rather than phenyl groups. An electronic effect of sterically similar aromatic substituents was investigated through NMR and DFT studies, showing that electron rich aryl groups allow better Cu-coordination. An interaction between the metal center and an aromatic group is responsible for this enhanced affinity and leads to a more tightly-coordinated transition structure leading to the major enantiomer. These studies illustrate the use of parametric quantitative structure-selectivity relationships to generate mechanistic models for asymmetric induction and catalyst structures that may be further probed by experiment and computation. This integrated approach leads to the rational modification of chiral ligands to achieve enhanced levels of selectivity.
Alkenes are among the most readily available organic molecules, and are feedstocks for the preparation of many commodity chemicals.  Using alkenes as starting materials in synthesis is practical because they are inexpensive and easy to handle. We recently reported  that alkenes can be used as the equivalents to premade alkyl metal species in coppercatalyzed asymmetric conjugate additions (ACA).  In these reactions hydrometalation (HM) of terminal alkenes with the Schwartz reagent  generates alkylzirconocenes,  which undergo asymmetric 1,4-additions catalyzed by complex A (Scheme 1). These processes are currently limited to the formation of tertiary centers from ACA to unsubstituted cyclic enones.  Herein we report that this approach can be used to form quaternary centers. Scheme 1. Hydrometalation/asymmetric conjugate addition of alkenes. Cp = cyclopentadienyl, Tf = trifluoromethanesulfonyl, TMS = trimethylsilyl.
Catalytic asymmetric conjugate addition reactions with organometallic reagents are powerful reactions in synthetic chemistry. Procedures that use non-stabilized carbanions have been developed extensively, but these suffer from a number of limitations that prevent their use in many situations. Here, we report that alkylmetal species generated in situ from alkenes can be used in highly enantioselective 1,4-addition initiated by a copper catalyst. Using alkenes as starting materials is desirable because they are readily available and have favourable properties when compared to pre-made organometallics. High levels of enantioselectivity are observed at room temperature in a range of solvents, and the reaction tolerates functional groups that are not compatible with comparable methods-a necessary prerequisite for efficient and protecting-group-free strategies for synthesis.
The expedient enantioselective synthesis of 5 bisabolane sesquiterpenes has been achieved using a common, one-pot lithiation-borylation reaction of secondary benzylic carbamates and either protodeboronation or oxidation to give the natural products in fewer than 5 steps, with high yield and >94 : 6 er.
Catalytic asymmetric conjugate addition reactions of alkylzirconium species to acyclic enones are reported. The alkylzirconium nucleophiles are generated in situ by hydrozirconation of alkenes with the Schwartz reagent. The reaction proceeds under mild and convenient conditions. A variety of functionalized nucleophiles can be used, and the method tolerates some variation in enone scope. The method uses a new chiral nonracemic phosphoramidite ligand in a complex with copper triflate.
Copper catalysis allows alkyl zirconium species, generated in situ from alkenes, to undergo conjugate addition reactions. A hydrometallation-catalytic asymmetric 1,4-addition was used to synthesize either enantiomer of a natural product in one step from commercially available materials. Hydrometallation-addition sequences applied to steroids containing a cross-conjugated dienone or 1,6-acceptor give highly functionalized products.
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