177329-71-4

Usage

Uses

Used in Organic Synthesis:
2-(t-Butyldimethylsilyloxy)-4-bromoanisole is used as a protecting group for hydroxyl groups during the synthesis of complex organic molecules. It serves to shield these groups from unwanted reactions, ensuring that specific transformations can be carried out without affecting other functional groups present in the molecule.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 2-(t-Butyldimethylsilyloxy)-4-bromoanisole is used as a synthetic intermediate for the development of various drugs. Its ability to protect hydroxyl groups allows chemists to create complex molecular structures with greater precision and control, leading to the production of more effective and targeted medications.
Used in Chemical Research:
2-(t-Butyldimethylsilyloxy)-4-bromoanisole is also employed in chemical research as a reagent for studying the properties and reactions of hydroxyl groups. Its use in protecting these groups enables researchers to gain a deeper understanding of the role of hydroxyl groups in various chemical processes and reactions.
Overall, 2-(t-Butyldimethylsilyloxy)-4-bromoanisole plays a crucial role in the fields of organic synthesis, pharmaceutical development, and chemical research, providing a valuable tool for the protection and manipulation of hydroxyl groups in a wide range of applications.

Upstream product

• 90-05-1 2-methoxy-phenol 
• 7368-78-7 4-bromoguaiacol 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 25016-01-7 5-bromo-2-methoxybenzaldehyde 
• 37942-01-1 5-bromo-2-methoxyphenol 

Downstream Products

• 185698-54-8 2-[3-(tert-butyldimethylsilyloxy)-4-methoxyphenyl]-1-(3,4,5-trimethoxyphenyl)ethyne 
• 900152-53-6 [3-[tert-butyl(dimethyl)silyl]oxy-4-methoxyphenyl]boronic acid 
• 1067880-31-2 isocombretastatin A₄ 
• 1189545-68-3 5-{[3-(tert-butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-hydroxy-methyl}-2-chloro-benzenesulfonamide 
• 185698-55-9 2-(3-hydroxy-4-methoxyphenyl)-1-(3',4',5'-trimethoxyphenyl)ethyne 
• 121042-95-3 (Z)-5-(3-tert-butyldimethylsilyloxy-4-methoxystyryl)-1,2,3-trimethoxybenzene 
• 117048-62-1 combrestatin A₄ 
• 612481-30-8 (2aS,4R,4aR,7aR,7bR)-2-[3-(tert-Butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-5-methylene-4-vinyl-decahydro-indeno[7,1-bc]furan-2-ol 
• 97315-21-4 (R)-2-(3-tert-butyldimethylsilyloxy-4-methoxy)phenyl-1-(3,4,5-trimethoxyphenyl)ethanol 
• 1189545-69-4 5-[3-(tert-butyl-dimethyl-silanyloxy)-4-methoxy-benzoyl]-2-chloro-benzenesulfonamide 
• 1189543-91-6 2-chloro-5-(3-hydroxy-4-methoxy-benzoyl)-benzenesulfonamide 

Relevant academic research and scientific papers

The synthesis and evaluation of temperature sensitive tubulin toxins

The synthesis of several potent inhibitors of tubulin polymerization that exert their activities through interaction at the colchicine binding site is described. These agents were evaluated for their abilities to inhibit the polymerization of tubulin and the growth of neoplastic cell cultures. Additionally, the inhibition of tubulin polymerization activity of these agents was assessed over a temperature range of 30-45°C to ascertain the effect of temperature on this activity. Several of the compounds possess significant inhibition of tubulin polymerization activity, and select compounds exhibit this activity in a temperature dependent manner.

Preparation method of pyran[3,2-a]carbazole compound

The invention relates to a preparation method of a pyran[3,2-a]carbazole compound represented by the formula (I). The preparation method comprises following steps: step one, taking 5-nitro-phenol as raw material to synthesize 3-(3'-3'-dimethylbutyne ether)-nitrobenzene; step two, preparing pyran[3,2-a]nitrobenzene from 3-(3'-3'-dimethylbutyne ether)-nitrobenzene through 3,3-sigma migration reactions between terminal alkyne hydrogen and a benzene ring system; step three, reducing pyran[3,2-a]nitrobenzene to obtain pyran[3,2-a]aniline; step four, preparing pyran[3,2-a]diphenylamine from pyran[3,2-a]aniline and aryl halide; and step five, preparing the pyran[3,2-a]carbazole compound from pyran[3,2-a]diphenylamine. The provided preparation method has the advantages that the steps of the synthesis route are few, the reaction conditions are mild, the adverse reactions are effectively reduced, the substrate universality is good, and the yield of target compound is high.

Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors

Recently, a series of selective human carboxylesterase inhibitors have been identified based upon the tanshinones, with biologically active molecules containing a 1,2-dione group as part of a naphthoquinone core. Unfortunately, the synthesis of such compounds is complex. Here we describe a novel method for the generation of 1,2-dione containing diterpenoids using a unified approach, by which boronic acids are joined to vinyl bromo-cyclohexene derivatives via Suzuki coupling, followed by electrocyclization and oxidation to the o-phenanthroquinones. This has allowed the construction of a panel of miltirone analogues containing an array of substituents (methyl, isopropyl, fluorine, methoxy) which have been used to develop preliminary SAR with the two human carboxylesterase isoforms. As a consequence, we have synthesized highly potent inhibitors of these enzymes (Ki 15 nM), that maintain the core tanshinone scaffold. Hence, we have developed a facile and reproducible method for the synthesis of abietane analogues that have resulted in a panel of miltirone derivatives that will be useful tool compounds to assess carboxylesterase biology.

Structural revision of the hancock alkaloid (-)-galipeine

The 1H and 13C NMR data of synthetic samples of (S)-N1-methyl-2- [2′-(3″-hydroxy-4″-methoxyphenyl)ethyl]-1,2,3,4-tetrahydroquinoline, the originally proposed structure of the Hancock alkaloid (-)-galipeine, do not match those of the natural product. Herein, the preparation of the regioisomer (S)-N1-methyl-2-[2′- (3″-methoxy-4″-hydroxyphenyl)ethyl]-1,2,3,4-tetrahydroquinoline is reported, the 1H and 13C NMR data of which are in excellent agreement with those of (-)-galipeine. Comparison of specific rotation data enables assignment of the absolute (S)- configuration of the alkaloid, and together, these data engender the structural revision of (-)-galipeine to (S)-N1-methyl-2-[2′-(3″-methoxy-4″-hydroxyphenyl)ethyl]- 1,2,3,4-tetrahydroquinoline.

Constructing novel dihydrofuran and dihydroisoxazole analogues of isocombretastatin-4 as tubulin polymerization inhibitors through [3+2] reactions

[3+2] reactions play a key role in constructing various pharmaceutical moleculars. In this study, using Mn(OAc)3 mediated and 1,3-dipolar [3+2] cyclization reactions, 38 novel dihydrofuran and dihydroisoxazole analogues of isoCA-4 were synthesized as inhibitors of tubulin polymerization. Among them, compound 6g was found to be the most potent cytotoxic agents against PC-3 cells with IC50 value of 0.47 μM, and compound 5p exhibted highest activity on HeLa cells with IC50 vaule of 2.32 μM. Tubulin polymerization assay revealed that 6g was a dose-dependent and effective inhibitor of tubulin assembly. Immunohistochemistry studies and cell cycle distribution analysis indicated that 6g severely disrupted microtubule network and significantly arrested most cells in the G2/M phase of the cell cycle in PC-3 cells. In addition, molecular docking studies showed that two chiral isomers of 6g can bind efficiently and similarly at colchicine binding site of tubulin.

TUBULIN BINDING AGENTS

The invention provides combretastatin A-4 like compounds that are modified to have enhanced tubulin binding activity and in some embodiments the ability to promote accumulation in the vasculature undergoing angiogenesis (homing activity). The compounds are based on the combretastatin A-4 skeletal structure having a tubulin-binding pharmacophore comprising two fused rings (A and B rings) in which the B ring is substituted with (a) an aromatic ring structure (C ring) and (b) a second substituent/functional group that comes off the B ring. The aromatic ring structure is typically a six membered ring phenolic or aniline structure, or may also be a fused ring structure such as a substituted or unsubstituted naphthalene. The second substituent on the B ring may for example be a substituent which has been found to provide enhanced tubulin binding activity (for example a carbonyl group), or may be a substituent that facilitates functionalisation of the B ring (for example an hydroxyl or amine group), or it may be a binding agent for a target that is preferentially expressed on vasculature undergoing angiogenesis, and not expressed on quiescent vasculature.

ARYLSULFONAMIDE-BASED MATRIX METALLOPROTEASE INHIBITORS

The present invention provides a compound of formula (I):said compound is inhibitor of MMP-2, and/or MMP-8, and/or MMP-9, and/or MMP-12 and/or MMP-13, and thus can be employed for the treatment of a disorder or disease characterized by abnormal activity of MMP-2, and/or MMP-8, and/or MMP-9, and/or MMP-12 and/or MMP- 13. Accordingly, the compound of formula (I) can be used in treatment of disorders or diseases mediated by MMP-2, and/or MMP-8, and/or MMP-9, and/or MMP-12, and/or MMP- 13. Finally, the present invention also provides a pharmaceutical composition.

PHARMACEUTICAL COMPOUNDS

The invention provides a compound of the formula (I) or a salt, solvate, tautomer or N-oxide thereof; wherein A is a saturated hydrocarbon linker group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; L1 is a bond or a linker selected from C1-C4 alkenylene, C1-C4 alkynylene, -CONR’, -NR’CO, -S, -C(O)-, -C(NR11)-, -C(S)-, -N(R11)2, C(=CHR11), -SO- and -SO2-; or L1 together with t R16 forms and 8-12 membered fused bicyclic heteroaryl ring system; L3 is a bond or a linker selected from CONH and HNCO; provided that L1 and L3 cannot both be linkers simultaneously; and provided also that L1 and L3 cannot both be a bond simultaneously; R16 is an optionally substituted 5- to 12-membered monocyclic or bicyclic carbocyclic or heterocyclic ring; L2 is absent or is a linker selected from C]-C4 alkylene, Ci-C4 alkenylene, Ci-C4 alkynylene, -CONR’-, -NR’CO-, -O-, -S-, -C(O)-, C(=CHR11), C(S)-, -N(R11)2, C3-4 cycloalkanediyl, -SO- and -SO2-; R17 is absent or is C1-6 alkyl or an optionally substituted 5 to 12 membered carbocyclic or heterocyclic ring; provided that when R17 is absent, then L2 is also absent; and R2, R3, R4, R5, R11 and R’ are as defined in the claims.

Enantioselective synthesis of natural combretastatin

In a process which appears to be general for the enantioselective synthesis of oxysubstituted 1,2-diarylethanols, a 4-methoxy-3-silyloxyphenyllithium, obtained by bromine-lithium exchange from the corresponding aryl bromide and t-butyllithium, added selectively at the b-carbon of (S)-2,3,4-trimethoxyphenyloxirane, elaborated from the corresponding styrene via Sharpless asymmetric dihydroxylation, to afford an adduct from which natural (-)-combretastatin was obtained by desilylation.

Ethynylation of aryl halides by a modified Suzuki reaction: Application to the syntheses of combretastatin A-4, A-5 and lunularic acid

On treatment with trimethyl borate sodium acetylide undergoes a palladium-catalyzed cross coupling with functionalized aryl halides or triflates in reasonable to good yields. The ethynylarenes thus obtained serve as building blocks for the formation of the highly effective tubulin polymerization inhibitors combretastatin A-4 (1) and A-5 (2) as well as for the synthesis of the plant-growth regulator lunularic acid (36). VCH Verlagsgesellschaft mbH, 1996.