Tandem addition beta-lithiation-alkylation sequence on alpha,beta-unsaturated aldehydes.

A tandem reaction between (E)-cinnamaldehyde, 1a, and phenyllithium affording beta-substituted dihydrochalcones was recently reported. NMR spectroscopic studies on the reaction mixture, as well as isotopic exchange reactions and trapping of two intermediates, provide clues on the several mechanistic steps of this new reaction. Extended studies revealed that beta-alkyl-substituted alpha,beta-unsaturated aldehydes and aliphatic lithium reagents did not afford good yields of the tandem reaction products, while aromatic lithium reagents gave good results. The aggregation features of the aryllithium reagents and the extended charged delocalization effects are considered to promote beta-selectivity. This approach provides a convenient route for the synthesis of a wide variety of beta-alkyl-substituted dihydrochalcones.

Glucose metabolism in older adults: a study including subjects more than 80 years of age.

OBJECTIVE: This study was undertaken to understand the dynamics of glucose metabolism in healthy non-diabetic subjects older than age 80 (old-old) compared with subjects aged 61 to 79 (young-old), as well as to compare healthy older subjects with impaired glucose tolerance (IGT) with older subjects with normal glucose tolerance (NGT). DESIGN: A cross sectional, observational study. SETTING: A university hospital clinical research center. PARTICIPANTS: There were 28 community-dwelling adults, 10 older than age 80 and 18 aged 61 to 79. Thirteen of these people had NGT and 15 had IGT. Subjects were not taking any medication that interfered with glucose tolerance. MEASUREMENTS: Status of glucose tolerance was determined by an oral glucose tolerance test categorized as NGT or IGT according to WHO criteria. Insulin sensitivity (SI) and glucose effectiveness (SG) were assessed using a tolbutamide-assisted intravenous glucose tolerance test (IVGTT). The data were analyzed using the Minmod modeling program. Glucose tolerance (K(g)) and the acute insulin response to glucose (AIRg) were calculated from the IVGTT. RESULTS: There were no significant differences between the young-old and old-old in body mass index or in plasma glucose, insulin, or C-peptide levels in the fasting state or during the OGTT. Values for K(g), SI, SG, and AIRg from the IVGTT were similar in the two age groups. When the subjects were classified by glucose tolerance status, the subjects with NGT had age, gender, and body mass index similar to the subjects with IGT. Older people with IGT had a lower K(g) and tended to have higher fasting glucose and similar fasting insulin compared with people with NGT. IGT subjects had lower SI and tended to have lower SG. The AIRg in IGT subjects tended to be low rather than high when compared with older people with NGT. CONCLUSION: Otherwise healthy adults more than 80 years of age have measures of glucose metabolism similar to people aged 61 to 79. The presence of IGT in older adults is associated with insulin resistance, regardless of patient age. We hypothesize that the lack of pancreatic islet compensation for insulin resistance may contribute to impaired glucose tolerance in older adults.