Benzindene prostaglandins. Synthesis of optically pure 15-deoxy-U-68,215 and its enantiomer via a modified intramolecular Wadsworth-Emmons-Wittig reaction

Lin, Chiu Hong; Aristoff, Paul A.; Johnson, Paul D.; McGrath, James P.; Timko, Joseph M.; Robert, André

doi:10.1021/jo00234a016

Cited by 15 publications

(5 citation statements)

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“…Several solvents were tested (CH 2 Cl 2 , hexanes, ethyl acetate, ether, methanol, acetone, toluene, pentane, and THF) and while THF was found to crash out one of the minor impurities from the crude mixture, the rest, including triphenylphospine and triphenylphosphine oxide, appeared to still be present by TLC. After attempting the Appel method, a number of other methods were attempted, as depicted in Table 2: NBS/PPh 3 (Bates et al, 1986; Imperiali & Roy, 1995; Lytollis et al, 1995), TsCl in Et 3 N (Hahn et al, 1988; Huang et al, 1983), TsCl in pyridine (Paquette et al, 1985), SOCl 2 in pyridine (Lynch & Dailey, 1995), PBr 3 (Lin et al, 1987), TMSBr (Choi & Kohn, 1995), and SOBr 2 in pyridine (Tellier & Sauvêtre, 1995). All these methods either underwent no reaction (Entries 2, 3), were a complicated mixture of products by TLC (Entries 1, 5–8) or the potential product did not survive workup (Entry 4).…”

Section: Resultsmentioning

confidence: 99%

Novel bisphosphonates via castor oil

Fayer,

Rosen,

Cermak

et al. 2023

J Americ Oil Chem Soc

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Hydroxy fatty acids (HFAs) have long been a staple component of feedstock oils with uses ranging from motor oils to food to pharmaceuticals. Castor oil, which contains the HFA ricinoleic acid as its principal component, is the most widely used source of HFA in the world. In addition, bisphosphonates are a functional moiety that has been shown to display a variety of industrial applications, ranging from use in water softeners to osteoporosis drugs, primarily due to their affinity for the calcium ion. We have long been interested in the modification of ricinoleic acid from castor oil to phosphorus derivatives, including α‐hydroxy phosphonates and phosphonic acids, and have now accomplished the synthesis of a family of ricinoleic‐derived bisphosphonates: one that retains the cis alkene found in ricinoleic acid and one where the alkene has undergone hydrogenation. These compounds have been produced in high yields and high purity and the synthesis of these compounds is reported.

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Section: Resultsmentioning

confidence: 99%

Novel bisphosphonates via castor oil

Fayer,

Rosen,

Cermak

et al. 2023

J Americ Oil Chem Soc

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“…46 Those were subsequently brominated using PBr 3 yielding the required alkyl bromides 21a−r (Scheme 2). 47 In the next reaction step, the crude alkyl bromides (21a−r) were coupled with a hydroxylbenzoic acid methyl ester (22a or 22b) by Williamson ether synthesis using K 2 CO 3 as a base in dimethylformamide (DMF). 48 The products 23c−t were in most cases isolated in excellent yields of more than 80%, except for compound 23k (37%).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Development of Chromen-4-one Derivatives as (Ant)agonists for the Lipid-Activated G Protein-Coupled Receptor GPR55 with Tunable Efficacy

et al. 2019

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The lipid-activated G protein-coupled receptor (GPCR) GPR55 has been proposed as a drug target for the treatment of chronic diseases including inflammation, neurodegeneration, neuropathic pain, metabolic diseases, and cancer. A series of chromen-4-one-2-carboxylic acid derivatives was synthesized with the aim to obtain potent and selective ligands for GPR55 by (i) attachment of a variety of substituted 8-benzamido residues, (ii) substitution in position 6 by halogen atoms, and (iii) thioation of the 4-oxo function. The compounds were investigated in β-arrestin recruitment assays using enzyme complementation. Depending on the substitution pattern, a spectrum of efficacies was obtained ranging from (partial) agonists to antagonists. 6-Chloro-8-(3-((5-cyclohexylpentyl)oxy)benzamido)-4-oxo-4H-chromene-2-carboxylic acid (74, PSB-18251) displayed the highest efficacy of the series combined with high potency (EC50 0.196 μM). 6-Chloro-8-(3-(heptyloxy)benzamido)-4-oxo-4H-chromene-2-carboxylic acid (76, PSB-18337) exhibited higher potency (EC50 0.0400 μM) but lower efficacy (39%). Several GPR55 antagonists were discovered including 8-(3-(cyclohexylmethoxy)benzamido)-4-oxo-4H-chromene-2-carboxylic acid (57, PSB-18263) (IC50 8.23 μM) and 4-oxo-8-(3-phenethoxybenzamido)-4H-chromene-2-carboxylic acid (65, PSB-18270) (IC50 3.96 μM). These potent GPR55 agonists and antagonists showed high selectivity versus the related GPCRs GPR18 and GPR35 tested in the same assay system, while 8-(4-(4-cyclohexylbutoxy)benzamido)-6-fluoro-4-oxo-4H-chromene-2-carboxylic acid (84, PSB-18177) represents a dual GPR35/GPR55 antagonist (IC50 GPR55: 3.26 μM, GPR35: 2.57 μM). Binding studies of selected compounds at CB1 and CB2 receptors indicated GPR55 selectivity also versus CB receptors. The newly developed GPR55 (partial) agonists and antagonists will be useful tools for evaluating the suitability of GPR55 as a drug target.

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“…1-[( E )-Cinnamyloxy]but-2-yne (1k ) . This material was prepared using the general procedure from but-2-yn-1-ol and cinnamyl bromide in 86% yield. IR (neat): 2850, 2239, 1490 cm -1 .…”

Section: Methodsmentioning

confidence: 99%

Bicyclization of Enynes Using the Cp₂TiCl₂−Mg−BTC System: A Practical Method to Bicyclic Cyclopentenones

1998

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Bicyclic titanacycles 2 generated with the Cp 2 TiCl 2 -Mg-P(OEt) 3 system can be trapped with bis-(trichloromethyl) carbonate (BTC) to give bicyclic cyclopentenones 3 in good yields. The titanacycle 2m was isolated and well-identified. Bicyclization of enynes containing 1,2-disubstituted olefin by this method gave good results with excellent stereoselectivity.a Method A: CO, M ) Ti, Zr. Method B: R3SiCN, then HOAc or CuSO4, M ) Ti.

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Benzindene prostaglandins. Synthesis of optically pure 15-deoxy-U-68,215 and its enantiomer via a modified intramolecular Wadsworth-Emmons-Wittig reaction

Cited by 15 publications

References 1 publication

Novel bisphosphonates via castor oil

Novel bisphosphonates via castor oil

Development of Chromen-4-one Derivatives as (Ant)agonists for the Lipid-Activated G Protein-Coupled Receptor GPR55 with Tunable Efficacy

Bicyclization of Enynes Using the Cp₂TiCl₂−Mg−BTC System: A Practical Method to Bicyclic Cyclopentenones

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Benzindene prostaglandins. Synthesis of optically pure 15-deoxy-U-68,215 and its enantiomer via a modified intramolecular Wadsworth-Emmons-Wittig reaction

Cited by 15 publications

References 1 publication

Novel bisphosphonates via castor oil

Novel bisphosphonates via castor oil

Development of Chromen-4-one Derivatives as (Ant)agonists for the Lipid-Activated G Protein-Coupled Receptor GPR55 with Tunable Efficacy

Bicyclization of Enynes Using the Cp2TiCl2−Mg−BTC System: A Practical Method to Bicyclic Cyclopentenones

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Bicyclization of Enynes Using the Cp₂TiCl₂−Mg−BTC System: A Practical Method to Bicyclic Cyclopentenones