158744-37-7Relevant academic research and scientific papers
Synthesis and evaluation of hapalosin and analogs as MDR-reversing agents
O'Connell, Celeste E.,Salvato, Kathleen A.,Meng, Zhaoyang,Littlefield, Bruce A.,Schwartz, C. Eric
, p. 1541 - 1546 (2007/10/03)
The marine natural product hapalosin and 22 analogs, which incorporated systematic substituent deletions or variations, were prepared. These compounds were evaluated in a cell-based assay for both MDR-reversing activity and general cytotoxicity. Some substituent modifications resulted in lower cytotoxicities, but most structural changes were either detrimental to or did not seriously alter the MDR-reversing activity.
Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959
Parkes, Kevin E. B.,Bushnell, David J.,Crackett, Peter H.,Dunsdon, Stephen J.,Freeman, Andrew C.,et al.
, p. 3656 - 3664 (2007/10/02)
Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials.Six approaches for the large-scale synthesis of this compound have been studied.All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5.They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation.The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1.Kilogram quantities of Ro 31-8959 have been prepared using this route.
