An improved kilogram-scale preparation of atorvastatin calcium.

Background: If literature protocols are followed, conversion of an advanced ketal ester intermediate (available in kilogram quantities via a published Paal-Knorr synthesis) to cholesterol-lowering drug atorvastatin calcium is hampered by several process issues, particularly at the final stage where the hemi-calcium salt is obtained.

Results: We developed a high-yielding synthesis of atorvastatin calcium salt on 7 kg scale that affords >99.5% product purities by introducing the following key improvements: i.

Relationship of the variability of the heterochromatic regions of chromosomes 1, 9, 16, and Y to some anthropometric characteristics in children with embryopathies of unknown etiology and in children with Down syndrome.

The relationship between variability of the heterochromatic regions of chromosomes 1, 9, 16, and Y, and anthropometric characteristics (length and mass of body, shoulder diameter) in 70 children with embryopathies of unknown etiology and in 40 children with Down syndrome was studied. The positive statistically significant correlations of the C segment lengths of chromosomes 1, 9, 16, their sum included, and the above characteristics were found. The correlation coefficients of Y chromosome were not significant.

Heterochromatic regions on chromosomes 1, 9, 16, and Y in children with some disturbances occurring during embryo development.

Some reduction of C-segment lengths and their variability on chromosomes 1, 9, 16, and Y was exhibited by children who had had some disturbances at early stages of morphogenesis. The data obtained might suggest a certain activity of the heterochromatic regions during embryo development. Based on this data one may also suppose that reduction of the amount of heterochromatin might affect the normal morphogenetic processes.