262363-93-9Relevant academic research and scientific papers
Enantioselective synthesis of protected forms of (3R,5R)-5- hydroxypiperazic acid useful for synthesis
Depew, Kristopher M.,Kamenecka, Theodore M.,Danishefsky, Samuel J.
, p. 289 - 292 (2000)
Protected versions of (3R,5R)-5-hydroxypiperazic acid were synthesized enantioselectively in two novel ways. The first derives its chirality from D- glutamic acid while the second uses an Evans amination and a diastereoselective bromolactonization to esta
Discovery through total synthesis: A retrospective on the himastatin problem
Kamenecka, Theodore M.,Danishefsky, Samuel J.
, p. 41 - 63 (2007/10/03)
A total synthesis of a structure proposed for himastatin was accomplished. The non-identity of the fully synthetic material with himastatin necessitated a revision of the assigned structure. Confirmation of the revised stereostructure was subsequently confirmed through total synthesis. Among the achievements during this effort were i) stereospecific routes to both anti-cis and syn-cis pyrrolindoline substructures; ii) a practical synthesis to 5-hydroxypiperazic acid in enantiomerically pure form; iii) a Stille coupling leading to a complex bi-indole moiety,and iv) efficient protecting group management throughout the evolving depsipeptide domain. The outlines for a biological pharmacophore have been delineated. The alternating D- and L-substituents in the 6-mer as well as the biaryl linkage connecting the two identical subunits are critical for maintaining biological activity. This pattern is simulated in another antibiotic, and suggests a possible structural trend for future SAR investigations.
