1440545-59-4

Upstream product

• 18162-48-6 tert-butyldimethylsilyl chloride 
• 1044263-52-6 (4S,4'S,5'R,2'E)-3-[5'-hydroxy-2',4'-dimethyl-2'-hexenoyl]-4-isopropyl-1,3-oxazolidin-2-one 
• 75-77-4 chloro-trimethyl-silane 
• 1440545-72-1 (R)-4-benzyl-3-((2R,3R,6S,7R,E)-7-(((tert-butyl)dimethylsilyl)oxy)-3-hydroxy-2,4,6-trimethyloct-4-enoyl)oxazolidin-2-one 
• 1440545-57-2 C₁₈H₃₃NO₃Si 
• 1440545-70-9 (S)-3-((4S,5R,E)-5-(((tert-butyl)dimethylsilyl)oxy)-2,4-dimethylhex-2-enoyl)-4-isopropyloxazolidin-2-one 
• 1440545-71-0 (4S,5R,E)-5-(((tert-butyl)dimethylsilyl)oxy)-2,4-dimethylhex-2-en-1-ol 
• 1440545-58-3 (4S,5R,E)-5-(((tert-butyl)dimethylsilyl)oxy)-2,4-dimethylhex-2-enal 

Downstream Products

• 134869-15-1 lactimidomycin 

Relevant academic research and scientific papers

Synthesis and Biological Evaluation of Lactimidomycin and Its Analogues

The studies culminating in the total synthesis of the glutarimide-containing eukaryote translation elongation inhibitor lactimidomycin are described. The optimized synthetic route features a ZnII-mediated intramolecular Horner-Wadsworth-Emmons (HWE) reaction resulting in a highly stereoselective formation of the strained 12-membered macrolactone of lactimidomycin on a 423 mg scale. The presence of the E,Z-diene functionality was found to be key for effective macrocyclizations as a complete removal of these unsaturation units resulted in exclusive formation of the dimer rather than monocyclic enoate. The synthetic route features a late-stage installation of the glutarimide functionality via an asymmetric catalytic Mukaiyama aldol reaction, which allows for a quick generation of lactimidomycin homolog 55 containing two additional carbons in the glutarimide side chain. Similar to lactimidomycin, this analog was found to possess cytotoxicity against MDA-MB-231 breast cancer cells (GI50=1-3 μM) using in vitro 2D and 3D assays. Although lactimidomycin was found to be the most potent compound in terms of anticancer activity, 55 as well as truncated analogues 50-52 lacking the glutarimide side-chain were found to be significantly less toxic against human mammary epithelial cells.

Synthesis of eukaryotic translation elongation inhibitor lactimidomycin via Zn(II)-mediated horner-wadsworth-emmons macrocyclization

An enantioselective synthesis of potent eukaryotic translation elongation inhibitor lactimidomycin has been accomplished in 21 linear steps. This synthesis features a Zn(II)-mediated Horner-Wadsworth-Emmons reaction that could be executed on a large scale to provide the highly strained 12-membered lactimidomycin macrolactone.