331810-13-0

Basic information

• Product Name: 31,42-bis(trimethylsilylether)rapamycin
• Synonyms: 31,42-bis(trimethylsilylether)rapamycin
• CAS NO: 331810-13-0
• Molecular Weight: 1058.55
• Mol File: 331810-13-0.mol

Chemical Properties

• CAS DataBase Reference: 31,42-bis(trimethylsilylether)rapamycin(CAS DataBase Reference)
• NIST Chemistry Reference: 31,42-bis(trimethylsilylether)rapamycin(331810-13-0)
• EPA Substance Registry System: 31,42-bis(trimethylsilylether)rapamycin(331810-13-0)

Safety Data

• Hazardous Substances Data: 331810-13-0(Hazardous Substances Data)

Upstream product

• 75-77-4 chloro-trimethyl-silane 
• 150821-39-9 rapamycin 
• 53123-88-9 sirolimus 
• 331810-10-7 31-(trimethylsilylether)rapamycin 

Downstream Products

• 179076-04-1 31-(triethylsilylether)rapamycin 
• 331810-10-7 31-(trimethylsilylether)rapamycin 
• 572924-54-0 Ridaforolimus 
• 53123-88-9 sirolimus 
• 155435-45-3 31,42-bis(triethylsilylether)rapamycin 
• 1192722-01-2 42-O-(2-bromoacetyl)-31-O-trimethylsilyl-rapamycin 
• 143030-02-8 C₄₀-TBS-rap 
• 851077-42-4 azidoacetic acid rapamycin ester 

Relevant articles and documents

Selective substitution of 31/42-OH in rapamycin guided by an in situ ir technique

An in situ IR technique was applied in the selective synthesis of the key intermediate for rapamycin derivatives, which made the reaction endpoint easily defined. This technology solved a bothersome problem in the preparation of rapamycin derivatives, and

Everolimus intermediate, and preparation method and application thereof

The invention discloses an everolimus intermediate, and a preparation method and an application of the everolimus intermediate. A structure of the everolimus intermediate C is shown as formula (1) asshown in the specification. The preparation method comprises the following step: allowing 28-monosilicon protected rapamycin (an everolimus intermediate B) to react with trifluoromethanesulfonic acidsingle-protection glycol ester in the presence of organic base. The invention further discloses the application of the everolimus intermediate C. The preparation method of the everolimus intermediateis simple and high in yield; everolimus prepared from the intermediate can reduce side reactions; a technical operation procedure is simplified; the total yield is increased; the product quality is ensured; and therefore, the preparation method has better industrial application and popularization prospects.

Preparation method of everolimus

The invention discloses a preparation method of everolimus. The preparation method comprises the following step of performing deprotection reaction on an everolimus intermediate C. The preparation method of everolimus adopts a manner of regioselective protection of rapamycin 28-hydroxyl, so that the selectivity of a 40-hydroxyl alkylation reaction is improved; side reactions are reduced; a total yield of everolimus calculated from rapamycin can reach above 70%; compared with yields reported in available literatures, the yield is greatly increased; a technical operation procedure is simplified;the product quality is ensured; and the preparation method has better industrial application and popularization prospects.

Synthesis and anticancer activity of novel rapamycin C-28 containing triazole moiety compounds

Rapamycin is an mTOR allosteric inhibitor with multiple functions such as immunosuppressive, anticancer, and lifespan prolonging activities. Its C-43 semi-synthetic derivatives temsirolimus and everolimus have been used as mTOR targeting anticancer drugs

Intermediate of temsirolimus and preparation method thereof

The invention provides an intermediate of temsirolimus. The intermediate has better selectivity and higher yield when used for preparation of the temsirolimus. The intermediate provided by the invention has a structural formula which is described in the specification.

Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents

Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was facilely synthesized via Huisgen's reaction. The anticancer activity of these compounds was evaluated against the Caski, H1299, MGC-803, and H460 human cancer cell lines. Some of the derivatives (8a-e, 9a-e) appeared to have stronger activity than that of rapamycin; however, 4a-d and 5a-e failed to show potential anticancer activity. Compound 9e with a (2,4-dichlorophenylamino)methyl moiety on the triazole ring was the most active anticancer compound, which showed IC50 values of 6.05 (Caski), 7.89 (H1299), 25.88 (MGC-803), and 8.60 μM (H460). In addition, research on the mechanism showed that 9e was able to cause cell morphological changes and to induce apoptosis in the Caski cell line. Most importantly, 9e can decrease the phosphorylation of mTOR and of its downstream key proteins, S6 and P70S6K1, indicating that 9e can effectively inhibit the mTOR signaling pathway. Thus, it may have the potential to become a new mTOR inhibitor against various cancers. Novel rapamycin triazole hybrids were synthesized via Huisgen's reaction and their anticancer activities were evaluated against four human cancer cell lines. Compound 9e with a (2,4-dichlorophenylamino)methyl moiety on the triazole ring showed the highest anticancer activity (IC50 = 6.05-25.88 μM). Since 9e can also inhibit the mTOR signaling pathway, it may become a new mTOR inhibitor against various cancers.

Rapamycin derivative, preparation method, pharmaceutical composition and uses thereof

The present invention belongs to the field of medicine and chemical industry, and relates to a rapamycin derivative represented by a formula I, a preparation method, a pharmaceutical composition and uses thereof. According to the compound of the present i

Method for preparing everolimus

The invention discloses a method for preparing everolimus. The method includes the following steps that rapamycin and trimethylchlorosilane react so as to achieve double protection of hydroxyl groups in positions 31 and 40, and acidic hydrolysis is conducted to obtain an intermediate 1 with the protected hydroxyl group in the position 31; the intermediate 1 and ethylene oxide have a condensation reaction to obtain an intermediate 2, the intermediate 2 is subjected to acidic hydrolysis to obtain an everolimus crude product, and the crude product is separated and purified by means of a preparation liquid phase to obtain everolimus.

METHOD FOR PREPARING 42-(DIMETHYLPHOSPHINATE) RAPAMYCIN

A method for preparing 42-(dimethylphosphinate) Rapamycin (Ridaforolimus) (I) is provided, which has advantages of high conversion rate and no 31,42-bis(dimethyl phosphinate) Rapamycin (III) generated. In the method of the present invention, Rapamycin (II) is firstly reacted with triethyl chlorosilane in a base condition to form 31,42-bis(triethylsilylether) Rapamycin (IV-b), followed by a selective deprotection process to obtain 31-triethylsilylether Rapamycin (V-b). Next, a phosphorylation reaction is performed by using dimethylphosphinic chloride under a base solution to obtain a crude product. Finally, a deprotection reaction is performed in a diluted sulfuric acid solution to obtain a crude product of Ridaforolimus (I). Since the conversion rate of each step of the method of the present invention is higher than 98%, it indicates that the method of the present invention is suitable for industrial production.

A Novel Rapamycin-polymer conjugate based on a new poly(Ethylene Glycol) multiblock copolymer

Purpose: Rapamycin has demonstrated potent anti-tumor activity in preclinical and clinical studies. However, the clinical development of its formulations was hampered due to its poor solubility and undesirable distribution in vivo. Chemical modification of rapamycin presents an opportunity for overcoming the obstacles and improving its therapeutic index. The objective of this study is to develop a drug-polymer conjugate to increase the solubility and cellular uptake of rapamycin. Methods: We developed the rapamycin-polymer conjugate using a novel, linear, poly(ethylene glycol) (PEG) based multiblock copolymer. Cytotoxicity and cellular uptake of the rapamycin-polymer conjugate were evaluated in various cancer cells. Results: The rapamycin-polymer conjugate provides enhanced solubility in water compared with free rapamycin and shows profound activity against a panel of human cancer cell lines. The rapamycin-polymer conjugate also presents high drug loading capacity (wt% ~ 26%) when GlyGlyGly is used as a linker. Cellular uptake of the conjugate was confirmed by confocal microscopic examination of PC-3 cells that were cultured in the presence of FITC-labled polymer (FITC-polymer). Conclusion: This study suggests that the rapamycin-polymer conjugate is a novel anti-cancer agent that may provide an attractive strategy for treatment of a wide variety of tumors.