1508307-50-3

Upstream product

• 327156-95-6 ((1s,4s)-4-((tert-butoxycarbonyl)amino)cyclohexyl)acetic acid 
• 1508307-49-0 C₈H₁₇NO 
• 1069120-19-9 tert-butyl ((1s,4s)-4-(2-hydroxyethyl)cyclohexyl)carbamate 

Downstream Products

• 1613337-69-1 C₈H₁₃N₃O 
• 1508307-51-4 (E)-ethyl 4-((1s,4s)-4-azidocyclohexyl)-2-methylbut-2-enoate 
• 1508307-52-5 (E)-4-((1s,4s)-4-azidocyclohexyl)-2-methylbut-2-en-1-ol 
• 1508307-53-6 (E)-4-((1s,4s)-4-azidocyclohexyl)-2-methylbut-2-enal 
• 1508307-54-7 (3R,7S)-7-((1E,3E)-5-((1s,4s)-4-azidocyclohexyl)-3-methylpenta-1,3-dien-1-yl)-5,5-dimethyl-1,6-dioxaspiro[2.5]octane 
• 1069120-27-9 (S,Z)-4-((tert-butyldimethylsilyl)oxy)-N-((1s,4s)-4-((2E,4E)-5-((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dien-1-yl)cyclohexyl)pent-2-enamide 
• 1197054-30-0 (S,Z)-5-(((1s,4s)-4-((2E,4E)-5-((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dien-1-yl)cyclohexyl)amino)-5-oxopent-3-en-2-yl(4-nitrophenyl)carbonate 
• 1510837-66-7 (S,Z)-5-(((1s,4s)-4-((2E,4E)-5-((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dien-1-yl)cyclohexyl)-amino)-5-oxopent-3-en-2-yl dimethylcarbamate 
• 1069120-28-0 (S,Z)-N-((1s,4s)-4-((2E,4E)-5-((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dien-1-yl)cyclohexyl)-4-hydroxypent-2-enamide 

Relevant academic research and scientific papers

Optimization of antitumor modulators of pre-mRNA splicing

The spliceosome regulates pre-mRNA splicing, which is a critical process in normal mammalian cells. Recently, recurrent mutations in numerous spliceosomal proteins have been associated with a number of cancers. Previously, natural product antitumor agents have been shown to interact with one of the proteins that is subject to recurrent mutations (SF3B1). We report the optimization of a class of tumor-selective spliceosome modulators that demonstrate significant in vivo antitumor activity. This optimization culminated in the discovery of sudemycin D6, which shows potent cytotoxic activity in the melanoma line SK-MEL-2 (IC50 = 39 nM) and other tumor cell lines, including JeKo-1 (IC50 = 22 nM), HeLa (IC50 = 50 nM), and SK-N-AS (IC 50 = 81 nM). We also report improved processes for the synthesis of these compounds. Our work supports the idea that sudemycin D6 is worthy of further investigation as a novel preclinical anticancer agent with application in the treatment of numerous human cancers.