Synthesis of methoxy and hydroxy containing tetralones: versatile intermediates for the preparation of biologically relevant molecules

Ghatak, Anjan; Dorsey, James M.; Garner, Charles M.; Pinney, Kevin G.

doi:10.1016/s0040-4039(03)00715-9

Cited by 22 publications

(22 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The solvent was removed under reduced pressure and the resulting residue was purified by flash chromatography [silica gel 200-400 mesh, eluent with a mixture of 1:1 hexanes: EtOAc] to afford 15 (3.9 g, 20 mmol, 94%) as a yellow oil. 1 …”

Section: -(Triisopropylsililoxy)-1-(2-methoxy-3-methylphenyl)butane-mentioning

confidence: 99%

“…Using the general procedure described for 3b, the 1,2,3,4-tetrahydro-5-methoxy-6-methylnaphthalen-1-one (9a) (0.36g, 1.9 mmol) was converted into 9b (0.34 g, 1.8 mmol, 95%); 1 …”

Section: 234-tetrahydro-5-methoxy-6-methylnaphthalen-1-ol (9b)mentioning

confidence: 99%

“…[1][2][3][4] Therefore, many efforts have been dedicated to search for reactions that can furnish homochiral α-tetralols. There are several reports dealing with the asymmetric hydrogenation of the α-tetralone itself, [5][6][7][8][9][10][11] as well as with its bioreduction, using either isolated enzymes or microorganisms.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Bioreduction of substituted a-tetralones promoted by Daucus carota root

Ferraz¹,

Bianco²,

Bombonato³

et al. 2008

Quím. Nova

View full text Add to dashboard Cite

Recebido em 15/1/08; aceito em 27/2/08; publicado na web em 2/4/09The bioreduction of a series of substituted α-tetralones, carried out using Daucus carota root (carrot), afforded the corresponding homochiral α-tetralols in variable conversions (9 to 90%) and excellent enantiomeric excesses. Two of the assayed α-tetralones were resistant to the bioreduction conditions. The absolute configurations of four α-tetralols were assigned as being (S), by comparison to the (S)-enantiomers obtained by kinetic resolution promoted by CALB-catalysed acetylation. Additionally, the new 5-methoxy-6-methyl-1-tetralone was synthesized in seven steps from 3-methylsalicylic acid.

show abstract

Section: -(Triisopropylsililoxy)-1-(2-methoxy-3-methylphenyl)butane-mentioning

confidence: 99%

“…Using the general procedure described for 3b, the 1,2,3,4-tetrahydro-5-methoxy-6-methylnaphthalen-1-one (9a) (0.36g, 1.9 mmol) was converted into 9b (0.34 g, 1.8 mmol, 95%); 1 …”

Section: 234-tetrahydro-5-methoxy-6-methylnaphthalen-1-ol (9b)mentioning

confidence: 99%

See 1 more Smart Citation

Bioreduction of substituted a-tetralones promoted by Daucus carota root

Ferraz¹,

Bianco²,

Bombonato³

et al. 2008

Quím. Nova

View full text Add to dashboard Cite

show abstract

“…18-20 This exploration was guided, in part, by the molecular structures of colchicine and certain members of the combretastatin family of natural products along with our previously discovered dihydronaphthalene-based analogues 18,21,22 (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

“…31-33 Efforts to mimic the combretastatin molecular-framework and optimize a wide-variety of biological parameters, resulted in a cadre of structural modifications. 34,35 A very limited sub-set of these molecules that were inspired by the combretastatins include benzophenone, 36,37 dihydronaphthalene, 18,21-23,38,39 indole, 40-43 and benzosuberene 18,19,20,44 analogues in which a single sp 2 hybridized carbon atom bridges the two aromatic rings and maintains the pseudo cis -orientation 45 that is important for enhanced biological activity. Two such benzosuberene-based compounds, referred to as KGP18 (phenol-based) 18,20,46 and KGP156 (amine-based), 19 have emerged as potential pre-clinical candidates (Fig.…”

Section: Introductionmentioning

confidence: 99%

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

Tanpure

George

Strecker

et al. 2013

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

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 M) and strongly cytotoxic against selected human cancer cell lines (for example, GI50 = 5.47 nM against NCI-H460 cells with fluorobenzosuberene 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.

show abstract