253128-15-3

Usage

Uses

As the provided materials do not specify any particular uses for (1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,35R,36S)-20-[2(S),3-Dihydroxypropyl]-21-methoxy-14-methyl-8,15-dimethylene-2,19,30,34,37,39,40,41-octaoxanonacyclo[24.9.2.1(3,32).1(3,33).1(6,9).1(12,16).0(18,22).0(29,36).0(31,35)]hentetracontan-24, it is not possible to list its applications based on the given information. However, given the compound's complex structure and the presence of various functional groups, it may have potential applications in fields such as pharmaceuticals, materials science, or as a synthetic intermediate in organic chemistry. Further research and experimentation would be necessary to explore and confirm its specific uses.

Upstream product

• 929121-23-3 (1R,2S,3S,4S,5S,6RS,11S,14S,17S,19R,21R,23S,25R,26R,27S,31R,34S)-25-[(2S)-2,3-dihydroxypropyl]-2,5-dihydroxy-26-methoxy-19-methyl-13,20-bis(methylene)-24,35,36,37,38,39-hexaoxaheptacyclo[29.3.1.1^3,6.14,34.1^11,14.1^17,21.0^23,27] nonatriacontane-8,29-dione 
• 728043-99-0 ((1R,2S,3S,4S,5S,6R,11S,14S,17S,19R,21R,23S,25R,26R,27S,31R,34S)-25-[(2S)-2,3-bishydroxypropyl]-2,5-bishydroxy-26-methoxy-19-methyl-13,20-bismethylidene-24,35,36,37,38,39-hexaoxaheptacyclo[29.3.1.1^3,6.1^4,34.11^1,14.1^17,21.0^23,27]nonatriacontane-8,29-dione) 

Downstream Products

• 253128-17-5 eribulin tosylate 
• 1297302-40-9 C₄₇H₆₃N₃O₁₁ 
• 253128-42-6 C₄₈H₆₃NO₁₃ 
• 253128-35-7 C₄₇H₆₄O₁₂S 
• 253128-34-6 C₄₆H₆₁ClO₁₁S 
• 253128-41-5 (1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-Amino-2-hydroxypropyl]-21-methoxy-14-methyl-8,15-bis(methylene)-2,19,30,34,37,39,40,41-octaoxanonacyclo [24.9.2.1^3,32.1^3,33.1^6,9.1^12,16.0^18,22.0^29,36.0^31,35]hentetracontan-24-one 

Relevant academic research and scientific papers

Commercial manufacture of halaven: Chemoselective transformations en route to structurally complex macrocyclic ketones

The evolution of the synthesis of Halaven (E7389, INN eribulin mesylate) from a medicinal chemistry process to the execution of the final process on pilot scale is described. The completion of the synthesis of Halaven from C1-C13 ester and C14-C35 sulfone alcohol involves a series of chemo-, regio-, and stereoselective transformations. Furthermore, a high-dilution macrocyclization presented a number of challenges for industrial-scale manufacture (throughput, processing time, and side reactions). This paper describes studies at Eisai leading to an understanding, optimization, and control of the chemistry that realized the reproducible commercial production of Halaven.

PROCESS FOR THE PREPARATION OF ERIBULIN MESYLATE INTERMEDIATE

The present application provides improved processes for the synthesis of eribulin intermediate, which generally comprise the steps of: a) De-protecting the eribulin-enone (compound 1) in tetrahydrofuran by using TBAF solution, buffered with imidazole HCl in the presence of molecular sieve and sodium sulphate to get an insitu mixture of eribulin-dione diastereomer at C12 carbon (compound 2). Then ketalization may be performed of eribulin-dione insitu intermediate containing mixture of diastereomer at C12 carbon (compound 2) with PPTS in dichloromethane to yield eribulin-diol (compound 3).

MACROCYCLIZATION REACTIONS AND INTERMEDIATES USEFUL IN THE SYNTHESIS OF ANALOGS OF HALICHONDRIN B

The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Horner-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

METHODS USEFUL IN THE SYNTHESIS OF HALICHONDRIN B ANALOGS

In general, the present invention features improved methods useful for the synthesis of analogs of halichondrin B, such as eribulin and pharmaceutically acceptable salts thereof (e.g., eribulin mesylate).

Macrocyclic ketone analogues of halichondrin B

Synthesis and SAR studies of structurally simplified analogues of marine natural product halichondrin B resulted in the discovery of E7389, a new potential antitumor agent currently undergoing Phase I clinical trials. Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product.

Intermediate compounds for preparing macrocylcic analogs

Intermediate compounds of the formulas for use in the preparation of macrocyclic analogs.