Asymmetric total syntheses of (+)- and (-)-spirotryprostatins A and B

2003 Spring.Includes bibliographical references.The first published total synthesis of (+)- and (-)-spirotryprostatin B is presented. The synthesis features an asymmetric azomethine ylide [1,3]-dipolar cycloaddition reaction. Additionally, a Barton-modified Hunsdiecker reaction was demonstrated as means of affecting an oxidative decarboxylation. Intermediates along the synthesis were studied for their biological activity as G2/M phase cell cycle inhibitors and microtubule assembly inhibitors. The asymmetric azomethine ylide [1,3]-dipolar cycloaddition was also studied in greater detail. Varying the aldehyde component of the reaction resulted in the formation three different cycloadducts. Theoretical calculations for the reaction were compared with observed results. Attempts to synthesize (-)-spirotryprostatin A are also presented. Two different strategies based on the synthesis of (+)- and (-)-spirotryprostatin B were explored

Flight 20 (STS-45) polysulfide gas path investigation

This report documents the results of the investigation into causes of gas paths on the 20A and 20B case-to-nozzle joints on STS-42. The investigation was conducted by the Investigation Board appointed by the senior vice president and general manager of Space Operations, Mr. R. E. Lindstrom, on 7 Feb. 1992. The probability of gas path occurrence in the nozzle-to-case-joint polysulfide had been identified during joint redesign. However, actual flight gas path incidence has been limited to RSRM-11 and the 20A and 20B segments. The blow-by condition on the 20A segment was a first time occurrence which was a special concern. The investigation covered all technical aspects associated with the gas path and blow-by conditions: materials and processing history, design requirements and as-built compliance to the design, thermal and structural analyses, computer modeling, and laboratory experimentation with the materials involved. The investigation was coordinated with Mr. Ken Jones at NASA Marshall in bi-weekly teleconferences. The Board also supported Dr. James C. Blair's independent NASA investigation team by providing copies of collected data, conducting requested analyses, and supporting several all-day teleconferences to provide understanding and resolve issues. The Dr. Blair support requirement was successfully concluded on 4 Mar. 1992

Tubulin-binding dibenz[c,e]oxepines: Part 2 Structural variation and biological evaluation as tumour vasculature disrupting agents

5,7-Dihydro-3,9,10,11-tetramethoxybenz[c,e]oxepin-4-ol 1, prepared from a dibenzyl ether precursor via Pd-catalysed intramolecular direct arylation, possesses broad-spectrum in vitro cytotoxicity towards various tumour cell lines, and induces vascular shutdown, necrosis and growth delay in tumour xenografts in mice at sub-toxic doses. The biological properties of 1 and related compounds can be attributed to their ability to inhibit microtubule assembly at the micromolar level, by binding reversibly to the same site of the tubulin αβ-heterodimer as colchicine 2 and the allocolchinol, N-acetylcolchinol 4