1069120-19-9

Upstream product

• 327156-95-6 ((1s,4s)-4-((tert-butoxycarbonyl)amino)cyclohexyl)acetic acid 

Downstream Products

• 847417-37-2 tert-butyl ((1s,4s)-4-(2-oxoethyl)cyclohexyl)carbamate 
• 1508307-49-0 C₈H₁₇NO 
• 1508307-50-3 2-((1s,4s)-4-azidocyclohexyl)ethanol 
• 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.

Antitumor compounds based on a natural product consensus pharmacophore

We report the design and highly enantioselective synthesis of a potent analogue of the spliceosome inhibitor FR901464, based on a non-natural product scaffold. The design of this compound was facilitated by a pharmacophore hypothesis that assumed key interaction types that are common to FR901464 and an otherwise unrelated natural product (pladienolide). The synthesis allows for the preparation of numerous novel analogues. We present results on the in vitro activity for this compound against several tumor cell lines.