75792-35-7

Usage

InChI:InChI=1/C11H14O3/c1-8(2)14-11-9(7-12)5-4-6-10(11)13-3/h4-8H,1-3H3

Upstream product

• 75-30-9 2-iodo-propane 
• 148-53-8 3-methoxy-2-hydroxybenzaldehyde 
• 75-26-3 isopropyl bromide 
• 99861-27-5 (2-isopropopoxy-3-methoxyphenyl)methanol 
• 1634-04-4 tert-butyl methyl ether 

Downstream Products

• 101115-65-5 2-isopropoxy-1-methoxy-3-(2-nitro-but-1-enyl)-benzene 
• 85686-10-8 2-isopropoxy-3-methoxybenzoic acid 
• 103275-75-8 2-isopropoxy-3-methoxyphenol 
• 197566-30-6 2-isopropoxy-1-methoxy-3-vinylbenzene 
• 568565-47-9 (2-isopropoxy-3-methoxy-phenyl)-(4-isopropoxy-phenyl)-methanol 
• 102472-54-8 Kohlensaeure-bis-(3-methoxy-2-isopropyloxy-phenylester) 
• 540492-28-2 (2-isopropoxy-3-methoxyphenyl)acetylene 

Relevant academic research and scientific papers

BENZOSUBERENE ANALOGUES AND RELATED COMPOUNDS WITH ACTIVITY AS ANTICANCER AGENTS

A series of benzosuberene analogues demonstrate effective inhibition of tubulin polymerization, cytotoxicity against human cancer cell lines, and vascular disruption in tumors.

Structure Guided Design, Synthesis, and Biological Evaluation of Novel Benzosuberene Analogues as Inhibitors of Tubulin Polymerization

A promising design paradigm for small-molecule inhibitors of tubulin polymerization that bind to the colchicine site draws structural inspiration from the natural products colchicine and combretastatin A-4 (CA4). Our previous studies with benzocycloalkeny

Efficient synthetic methodology for the construction of dihydronaphthalene and benzosuberene molecular frameworks

Benzosuberene analogues (1 and 2) and dihydronaphthalene analogues (3 and 4) function as potent inhibitors of tubulin polymerization, demonstrate pronounced cytotoxicity (low nM to pM range) against human cancer cell lines, and are promising vascular disrupting agents (VDAs). As such, these compounds represent lead anticancer agents with potential translatability towards the clinic. Methodology previously established by us (and others) facilitated synthetic access to a variety of structural and functional group modifications necessary to explore structure activity relationship considerations directed towards the development of these (and related) molecules as potential therapeutic agents. During the course of these studies it became apparent that the availability of synthetic methodology to facilitate direct conversion of the phenolic-based compounds to their corresponding aniline congeners would be beneficial. Accordingly, modified synthetic routes toward these target phenols (benzosuberene 1 and dihydronaphthalene 3) were developed in order to improve scalability and overall yield [45-57% (1) and 32% (3)]. Moreover, benzosuberene-based phenolic analogue 1 and separately dihydronaphthalene-based phenolic analogue 3 were successfully converted into their corresponding aniline analogues 2 and 4 in good yield (>60% over three steps) using a palladium catalyzed amination reaction.

ATP3 and MTP3: Easily Prepared Stable Perruthenate Salts for Oxidation Applications in Synthesis

The Ley–Griffith tetra-n-propylammonium perruthenate (TPAP) catalyst has been widely deployed by the synthesis community, mainly for the oxidation of alcohols to aldehydes and ketones, but also for a variety of other synthetic transformations (e.g. diol cleavage, isomerizations, imine formation and heterocyclic synthesis). Such popularity has been forged on broad reaction scope, functional group tolerance, mild conditions, and commercial catalyst supply. However, the mild instability of TPAP creates preparation, storage, and reaction reproducibility issues, due to unpreventable slow decomposition. In search of attributes conducive to catalyst longevity an extensive range of novel perruthenate salts were prepared. Subsequent evaluation unearthed a set of readily synthesized, bench stable, phosphonium perruthenates (ATP3 and MTP3) that mirror the reactivity of TPAP, but avoid storage decomposition issues.

A synthetic BNC105 method

The invention relates to a method for compounding BNC 105, which uses o-vanillin and 3,4,5- trimethoxy-benzaldehyde as starting materials. The o-vanillin is subjected to hydroxy protection and aldehyde oxidation to be hydrolyzed into phenol, and the pheno

Selectivity Modulation of the Ley–Griffith TPAP Oxidation with N-Oxide Salts

A wide variety of novel non-hygroscopic N-oxide tetraphenylborate salts were synthesized and evaluated as co-oxidants in the Ley–Griffith (TPAP) oxidation of benzylic and allylic alcohols under non-anhydrous conditions. The novel DABCOO·TPB (2:1) salt was herein unearthed as a viable competitor to the first-generation NMO·TPB (2:1) salt, but more importantly gave increased performance under oxidative competition. X-ray crystal structure analysis and NMR spectroscopy revealed that depending on the crystallization conditions 1:1, 2:1 or 3:2 N-oxide–tetraphenylborate salts could be formed.

NMO·TPB: A selectivity variation on the Ley-Griffith TPAP oxidation

A non-hygroscopic tetraphenylborate salt of N-methylmorpholine-N-oxide (NMO) is reported (NMO·TPB), which modulates the standard Ley-Griffith oxidation such that benzylic and allylic alcohols are oxidised selectively. An attractive feature of this new protocol is that anhydrous conditions are not required for this selective tetra-n-propylammonium perruthenate (TPAP) oxidation, superseding the requirement of molecular sieves.

N,N,N′,N′-Tetramethylenediamine dioxide (TMEDAO2) facilitates atom economical/open atmosphere Ley-Griffith (TPAP) tandem oxidation-Wittig reactions

N,N,N′,N′-Tetramethylethylenediamine dioxide (TMEDAO2) was explored as a more atom economical co-oxidant for the Ley-Griffith oxidation of alcohols to aldehydes. TMEDAO2 was found to selectivity oxidise benzylic and allylic alcohols in comparable yields to that of the standard Ley-Griffith co-oxidant (NMO). Importantly TMEDAO2 facilitated tandem Ley-Griffith-Wittig reactions with stabilised ylides, in good to excellent yields, without the requirement of anhydrous conditions.

Synthesis of structurally diverse benzosuberene analogues and their biological evaluation as anti-cancer agents

Diversely functionalized, fused aryl-alkyl ring systems hold a prominent position as well-established molecular frameworks for a variety of anti-cancer agents. The benzosuberene (6,7 fused, also referred to as dihydro-5H-benzo[7] annulene and benzocycloheptene) ring system has emerged as a valuable molecular core component for the development of inhibitors of tubulin assembly, which function as antiproliferative anti-cancer agents and, in certain cases, as vascular disrupting agents (VDAs). Both a phenolic-based analogue (known as KGP18, compound 39) and its corresponding amine-based congener (referred to as KGP156, compound 45), which demonstrate strong inhibition of tubulin assembly (low micromolar range) and potent cytotoxicity (picomolar range for KGP18 and nanomolar range for KGP156) are noteworthy examples of such benzosuberene-based compounds. In order to extend the structure-activity relationship (SAR) knowledge base related to benzosuberene anti-cancer agents, a series of eleven analogues (including KGP18) were prepared in which the methoxylation pattern on the pendant aryl ring as well as functional group incorporation on the fused aryl ring were varied. The synthetic approach to these compounds featured a sequential Wittig olefination, reduction, Eaton's reagent-mediated cyclization strategy to achieve the core benzosuberone intermediate, and represented a higher-yielding synthesis of KGP18 (which we prepared previously through a ring-expansion strategy). Incorporation of a fluorine or chlorine atom at the 1-position of the fused aryl ring or replacement of one of the methoxy groups with hydrogen (on the pendant aryl ring of KGP18) led to benzosuberene analogues that were both strongly inhibitory against tubulin assembly (IC50 approximately 1.0 μM) and strongly cytotoxic against selected human cancer cell lines (for example, GI50 = 5.47 nM against NCI-H460 cells with fluoro-benzosuberene analogue 37). A water-soluble phosphate prodrug salt of KGP18 (referred to as KGP265, compound 44) and a water-soluble serinamide salt (compound 48) of KGP156 were also synthesized and evaluated in this study.

CHEMICAL PROCESSES FOR THE MANUFACTURE OF SUBSTITUTED BENZOFURANS

The present invention relates to the scaled-up synthesis of biologically active compounds which display useful therapeutic activity in treating proliferative disorders. In particular the invention relates to process methods for the kilogram scale synthesi