Total synthesis of (±)-lundurine B.

A total synthesis of (±)-lundurine B was accomplished. A combination of stereoselective intramolecular cyclopropane formation and aryl amination furnished cyclopropane-fused indoline stereoselectively. Ring-closing metathesis (RCM) of siloxy diene and intramolecular aminoacetal formation followed by bridgehead vinylation of an anti-Bredt iminium cation led to the construction of six- and seven-membered rings with a quaternary carbon center. After the formation of dihydropyrrole by RCM, the Boc-protecting group of indoline was converted into the corresponding methyl carbamate via silyl carbamate to complete the total synthesis of (±)-lundurine B. The characteristic rearrangement of the cyclopropane-fused indoline skeleton is also described.

Transgenic mice overexpressing soluble osteoclast differentiation factor (sODF) exhibit severe osteoporosis.

Osteoclast differentiation factor, ODF, also called RANKL, TRANCE, or OPGL, is a key molecule for osteoclast differentiation and activation, and is thought to act as a membrane-associated molecule in bone remodeling. Recent study suggested that soluble ODF (sODF) released from T cells also has some roles in bone resorption. To investigate the physiological and pathological function of sODF, we generated two types of transgenic mice overexpressing sODF. Mice overexpressing sODF ubiquitously from the early developmental stage died at the late fetal stage. The other type of mice, expressing sODF only in the liver after birth, grew to maturity with normal body size and weight. However, they exhibited a marked decrease in bone mineral density with aging compared with their non-transgenic littermates, and in addition, the strength of their femurs was extremely reduced. Histological analysis showed that the trabecular bone mass was decreased at 6 weeks of age and was sparse at age 3-4 months. The number of osteoclasts was significantly increased, while the number of osteoblasts was not altered on the surface of young trabecular bone. These results indicate that excessive production of sODF causes osteoporosis by accelerated osteoclastogenesis. The transgenic mouse overexpressing sODF in the liver could serve as a useful animal model for studying bone remodeling and evaluating therapeutic agents for osteoporosis.