Stereoselective synthesis of bicyclo[3.1.1]heptane derivatives via intramolecular photocycloaddition reaction.

Optically active 1,3-bridged cyclobutanes 10 of the bicyclo[3.1.1]heptane ring system and 1,2-bridged cyclobutanes 11 of the bicyclo[3.2.0]heptane ring system were produced by UV irradiation of alpha,beta,gamma,delta-unsaturated esters 9a and 9c-f. The preference of endo-stereochemistry at C-6 bridged head was observed in cross-adducts 10. On the other hand, irradiation of conjugated dienol 9b led via only parallel cycloaddition to 1,2-bridged cyclobutane 11.

Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation.

We analyzed the cause of agammaglobulinemia in a girl whose father had been diagnosed as having X-linked agammaglobulinemia (XLA). Flow cytometric analysis revealed the lack of peripheral B cells with the block of B-cell differentiation in the stages between pro-B cells and pre-B cells in the bone marrow, and the defect of the Bruton tyrosine kinase (BTK) expression on monocytes. We found a BTK gene mutation in the first single base pair of intron 11 in her father and heterozygous mutation in the patient at the site. Sequence analysis of abnormally smaller-sized polymerase chain reaction (PCR) products of cDNA confirmed splicing abnormalities due to the mutation. Maternally derived X chromosome was exclusively inactivated in peripheral blood and oral mucosal cells. This is the first report of female XLA caused by heterozygous BTK gene abnormality and extreme nonrandom inactivation of X chromosome on which normal BTK gene is located.