445493-23-2

Usage

Uses

Used in Pharmaceutical Industry:
11107B is used as a potent cancer cell growth inhibitor for targeting the SF3B1 subunit of the spliceosome. Its ability to inhibit cancer cell proliferation and disrupt hypoxia signals makes it a valuable compound in the development of novel cancer therapies.
Used in Anticancer Applications:
11107B is employed as an anticancer agent, particularly effective against various types of cancer. Its unique mechanism of action allows it to target the spliceosome, which is involved in the regulation of gene expression and cell growth. This makes 11107B a promising candidate for the development of new cancer treatments and potentially overcoming drug resistance in certain cases.
Used in Drug Delivery Systems:
To enhance the efficacy and bioavailability of 11107B, researchers are exploring various drug delivery systems. These systems aim to improve the compound's delivery to cancer cells, potentially increasing its therapeutic outcomes and reducing side effects. Novel drug delivery systems, such as organic and metallic nanoparticles, are being investigated for their ability to carry and release 11107B in a controlled manner, optimizing its anticancer properties.

Upstream product

• 1399680-13-7 C₄₈H₉₀O₈Si₃ 
• 934497-75-3 (2R,3S)-2-((2R,3R)-3-{(2S)-2-methyl-3-[(1-phenyl-1H-tetrazol-5-yl)sulfonyl]propyl}oxiran-2-yl)pentan-3-ol 
• 934497-74-2 (3S,4S,5E,8S)-4,8-dimethyl-9-[(1-phenyl-1H-tetrazol-5-yl)sulfonyl]non-5-en-3-ol 
• 1399680-07-9 (2S,6S,7S,E)-2,6-dimethyl-7-((triethylsilyl)oxy)non-4-en-1-yl methanesulfonate 
• 1399680-36-4 C₁₂H₂₄O₄S 
• 95273-27-1 (3S,4S)-4-hydroxy-3-methyl-1-hexene 
• 1399679-64-1 (S)-2-methylpent-4-en-1-yl methanesulfonate 
• 5673-98-3 (S)-(-)-2-methyl-4-penten-1-ol 
• 277297-37-7 (2S)-N-[1R,2R]-(2-hydroxy-1-methyl-2-phenylethyl)-N,2-dimethyl-4-pentenamide 
• 1399679-56-1 (E)-10-((tert-butyldimethylsilyl)oxy)-3,7-dimethyl-12-oxo-2-((E)-4-oxobut-2-en-2-yl)-7-((triethylsilyl)oxy)oxacyclododec-4-en-6-yl acetate 
• 1399679-51-6 5-(((S)-2-methyl-3-((2R,3R)-3-((2S,3S)-3-((triethylsilyl)oxy)pentan-2-yl)oxiran-2-yl)propyl)sulfonyl)-1-phenyl-1H-tetrazole 
• 1399680-31-9 (E)-10-((tert-butyldimethylsilyl)oxy)-2-((E)-4-hydroxybut-2-en-2-yl)-3,7-dimethyl-12-oxo-7-((triethylsilyl)oxy)oxacyclododec-4-en-6-yl acetate 
• 1399680-03-5 (E)-10-((tert-butyldimethylsilyl)oxy)-3,7-dimethyl-12-oxo-7-((triethylsilyl)oxy)-2-((E)-4-(trityloxy)but-2-en-2-yl)oxacyclododec-4-en-6-yl acetate 
• 1399680-29-5 (E)-4-((tert-butyldimethylsilyl)oxy)-8-hydroxy-7,11-dimethyl-7-((triethylsilyl)oxy)-12-((E)-4-(trityloxy)but-2-en-2-yl)oxacyclododec-9-en-2-one 

Downstream Products

• 934498-24-5 C₅₀H₆₂F₆O₁₂ 

Relevant academic research and scientific papers

Expedient Total Syntheses of Pladienolide-Derived Spliceosome Modulators

Atom and step economical total syntheses of spliceosome modulating natural products pladienolides A and B are described. The strategic functionalization of an unsaturated macrolide precursor enabled the most concise syntheses of these natural products to date and provides convenient, flexible access to stereodefined macrolides to streamline medicinal chemistry explorations. Notably, this synthetic route does not depend on protecting group manipulations that traditionally define synthesis planning for polyhydroxylated natural products of polyketide origin. Its utility is further demonstrated by the enantioselective total synthesis of H3B-8800, a hitherto semisynthetic pladienolide-derived spliceosome modulator undergoing clinical trials for hematological malignancies.

Synthesis of pladienolide b and its 7-epimer with insights into the role of the allylic acetate

Diastereomeric macrolactones 41 and 48, which are epimeric at C-7, were both prepared by a synthesis based on our previously developed route to the macrolactone core of pladienolide B. Both compounds contain all the functionality of the macrolactone core

Synthesis of Pladienolide B and Its 7-Epimer with Insights into the Role of the Allylic Acetate

Diastereomeric macrolactones 41 and 48, which are epimeric at C-7, were both prepared by a synthesis based on our previously developed route to the macrolactone core of pladienolide B. Both compounds contain all the functionality of the macrolactone core plus the vinyl iodide unit in the side chain. The key step to construct the seco acid for the macrolactonization was a Horner-Wadsworth-Emmons (HWE) reaction to produce acyclic enone 17. The required keto phosphonate for the HWE reaction was originally obtained from (R)-(-)-linalool. The derived macrolactone underwent a reduction of the enone function to give 7-epi-alcohol 20, and its acetylation, either under Mitsunobu or classical acylation conditions, produced allylic acetate 40. This represents a rare case in which a Mitsunobu reaction occurred with retention of configuration. The complete side chain that contains all the functionality was attached by a Stille cross-coupling reaction to lead to 7-epi-pladienolide B (42). To obtain pladienolide B (1), the reduction of acyclic enone 17 under chelation-controlled conditions [Zn(BH4)2, Et2O] gave allylic alcohol 43 with the correct configuration at C-7 with regard to the natural product. Conversion of this allylic alcohol to seco acid 46 followed by a Shiina macrolactonization afforded vinyl iodide 48. Its Stille coupling with vinylstannane 39 provided pladienolide B (1). Preliminary testing for cytotoxicity against the L929 cell line showed 7-epi-pladienolide B (42) to be completely inactive, which is in contrast to pladienolide B (1) that displayed an IC50 (half maximal inhibitory concentration) value of 7.5 nM. These results point to the importance of the correct configuration of the OAc functional group at C-7 of pladienolide B. Pladienolide B (1) and 7-epi-pladienolide B (42) were both prepared by the reduction of an enone precursor, that is, through a chelation-controlled reduction of an acyclic enone (for 1) or the reduction of a macrocyclic enone precursor (for 42). The correct configuration of the allylic acetate group at C-7 is crucial. Although synthetic 1 was highly cytotoxic, epimer 42 was completely inactive.

Enantioselective synthesis of pladienolide B and truncated analogues as new anticancer agents

An enantioselective synthesis of natural anticancer macrolide pladienolide B is described. The synthetic highlights include Sharpless asymmetric epoxidation, ring closing metathesis (RCM), Ireland-Claisen rearrangement, Shi epoxidation, and Pd-catalyzed S

Enantioselective total synthesis of pladienolide B: A potent spliceosome inhibitor

An enantioselective and convergent total synthesis of pladienolide B (1) is described. Pladienolide B binds to the SF3b complex of a spliceosome and inhibits mRNA splicing activity. The synthesis features an epoxide opening reaction, an asymmetric reduction of a β-keto ester, and a cross metathesis strategy for the side chain synthesis.

Process for total synthesis of pladienolide B and pladienolide D

[Problems to be Solved] To provide an effective process for total synthesis of pladienolide B and pladienolide D having excellent anti-tumor activity and to provide useful intermediates in the above-described process. [Measure for Solving the Problem] A process for producing a compound represented by Formula (11): wherein P1, P7, P8, P9 and R1 are the same as defined below, characterized by including reacting a compound represented by Formula (12): wherein P7 means a hydrogen atom or a protecting group for hydroxy group; R1 means a hydrogen atom or a hydroxy group, with a compound represented by Formula (13): wherein P1 means a hydrogen atom or a protecting group for hydroxy group; P8 means a hydrogen atom, an acetyl group or a protecting group for hydroxy group; P9 means a hydrogen atom or a protecting group for hydroxy group; or P8 and P9 may form together a group represented by a formula: wherein R5 means a phenyl group which may have a substituent, in the presence of a catalyst.

Total synthesis of the potent antitumor macrolides pladienolide B and D

Getting cross: The total syntheses of two pladienolides (see picture), which have prominent antitumor activity based on a unique mechanism of action, have been accomplished, and their absolute configurations were verified. The 12-membered aliphatic macrolide structure was formed by ring-closing metathesis, and the side-chain moiety was coupled to the macrolide by Julia-Kocienski olefination or cross-metathesis. (Chemical Equation Presented).