7475-92-5

Upstream product

• 13545-04-5 2,3-dimethylsuccinic acid 
• 75-36-5 acetyl chloride 
• 597-43-3 2,2-dimethylsuccinic acid 
• 201230-82-2 carbon monoxide 
• 5402-54-0 cis-α,β-dimethyl-β-propiolactone 
• 925669-95-0 2,3-cis-epoxybutane 
• 21490-63-1 2,3-trans-epoxybutane 

Downstream Products

• 854855-69-9 4-(4-isopropyl-phenyl)-2,3-dimethyl-4-oxo-butyric acid 
• 608-40-2 meso 2,3-dimethylsuccinic acid 
• 1134-40-3 2,3,6,7-tetramethylnaphthalene 
• 114090-95-8 cis-5,5-dibenzyl-3,4-dimethyldihydrofuran-2(3H)-one 
• 114090-95-8 trans-5,5-dibenzyl-3,4-dimethyldihydrofuran-2(3H)-one 
• 84374-90-3 ethyl (E)-cis-3,4-dimethyl-5-oxotetrahydrofuran-2-ylideneacetate 
• 84374-90-3 ethyl (Z)-cis-3,4-dimethyl-5-oxotetrahydrofuran-2-ylideneacetate 
• 84641-70-3 1-ethyl erythro-4,5-dimethyl-3-oxo-2-(triphenylphosphonio)hexadienoate 
• 13122-66-2 (2R*,3S*)-2,3-dimethyl-4-oxo-4-phenylbutanoic acid 
• 358369-08-1 4-(3,4-dimethoxyphenyl)-2,3-dimethyl-4-oxobutyric acid 
• 925687-73-6 2-(3-carboxy-2-methyl-butyrylamino)-benzoic acid 
• 925687-80-5 2,3-dimethyllycactonic acid 
• 21564-92-1 2,3-dimethyl-1,2,3,4-tetrahydro-1-naphthol 
• 34599-63-8 2,3-dimethyl-4-phenylbutanoic acid 

Relevant academic research and scientific papers

Catalytic double carbonylation of epoxides to succinic anhydrides: Catalyst discovery, reaction scope, and mechanism

The first catalytic method for the efficient conversion of epoxides to succinic anhydrides via one-pot double carbonylation is reported. This reaction occurs in two stages: first, the epoxide is carbonylated to a β-lactone, and then the β-lactone is subsequently carbonylated to a succinic anhydride. This reaction is made possible by the bimetallic catalyst [(CITPP)Al(THF)2]+[Co(CO)4]- (1; CITPP = meso-tetra(4-chlorophenyl)porphyrinato; THF = tetrahydrofuran), which is highly active and selective for both epoxide and lactone carbonylation, and by the identification of a solvent that facilitates both stages. The catalysis is compatible with substituted epoxides having aliphatic, aromatic, alkene, ether, ester, alcohol, nitrile, and amide functional groups. Disubstituted and enantiomerically pure anhydrides are synthesized from epoxides with excellent retention of stereochemical purity. The mechanism of epoxide double carbonylation with 1 was investigated by in situ IR spectroscopy, which reveals that the two carbonylation stages are sequential and non-overlapping, such that epoxide carbonylation goes to completion before any of the intermediate β-lactone is consumed. The rates of both epoxide and lactone carbonylation are independent of carbon monoxide pressure and are first-order in the concentration of 1. The stages differ in that the rate of epoxide carbonylation is independent of substrate concentration and first-order in donor solvent, whereas the rate of lactone carbonylation is first-order in lactone and inversely dependent on the concentration of donor solvent. The opposite solvent effects and substrate order for these two stages are rationalized in terms of different resting states and rate-determining steps for each carbonylation reaction.

Synthesis, nicotinic acetylcholine receptor binding, antinociceptive and seizure properties of methyllycaconitine analogs

A series of methyllycaconitine (1a, MLA) analogs was synthesized where the (S)-2-methylsuccinimidobenzoyl group in MLA was replaced with a (R)-2-methyl, 2,2-dimethyl-, 2,3-dimethyl, 2-phenyl-, and 2-cyclohexylsuccinimidobenzoyl (1b-f) group. The analogs 1b-f were evaluated for their inhibition of [125I]iodo-MLA binding at rat brain α7 nicotinic acetylcholine receptors (nAChR). In order to determine selectivity, MLA and the analogs 1b-f were evaluated for inhibition of binding to rat brain α,β nAChR using [3H]epibatidine. At the α7 nAChR, MLA showed a Ki value of 0.87 nM, analogs 1b-e possessed Ki values of 1.67-2.16 nM, and 1f showed a Ki value of 26.8 nM. Surprisingly, the analog 1e containing the large phenyl substituent (Ki = 1.67 nM) possessed the highest affinity. None of the compounds possessed appreciable affinity for α,β nAChRs. MLA antagonized nicotine-induced seizures with an AD50 = 2 mg/kg. None of the MLA analogs were as potent as MLA in this assay. MLA and all of the MLA analogs, with the exception of 1b, antagonized nicotine's antinociceptive effects in the tail-flick assay. Compound 1c (Ki = 1.78 nM at α7 nAChR) with an AD50 value of 1.8 mg/kg was 6.7 times more potent than MLA (AD50 = 12 mg/kg) in antagonizing nicotine's antinociceptive effects but was 5-fold less potent than MLA in blocking nicotine-induced seizures. Since MLA has been reported to show neuroprotection against β-amyloid1-42, these new analogs which have high α7 nAChR affinity and good selectivity relative to α,β nAChRs will be useful biological tools for studying the effects of α7 nAChR antagonist and neuroprotection.

Estrogen receptor ligands. Part 9: Dihydrobenzoxathiin SERAMs with alkyl substituted pyrrolidine side chains and linkers

A series of benzoxathiin SERAMs was prepared. Minor modifications in the side chain or linker resulted in significant effects on biological activity, especially in uterine tissue. A series of dihydrobenzoxathiin SERAMs with alkylated pyrrolidine side chains or alkylated linkers was prepared. Minor modifications in the side chain or linker resulted in significant effects on biological activity, especially in uterine tissue.

Catalytic carbonylation of β-lactones to succinic anhydrides

A well-defined,highly active and selective catalyst for the synthesis of succinic anhydrides from CO and β-lactones is reported. At 200 psi of CO, the catalyst [(N,N′-bis(3,5-di-tert-butylsalicylidene)phenylenediamino)Al(THF)2][Co(CO)4] carbonylates β-propiolactones to succinic anhydrides in high yield. (R)-β-Butyrolactone is carbonylated to (S)-methylsuccinic anhydride with clean inversion of stereochemistry, while cis-2,3-dimethyl-β-propiolactone yields exclusively trans-2,3-dimethylsuccinic anhydride. These data are consistent with a mechanism involving nucleophilic attack by [Co(CO)4]- on the β carbon of the lactone, followed by CO insertion and anhydride formation. Copyright

ESTROGEN RECEPTOR MODULATORS

The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or preven

Process for the preparation of α-methylene-γ-butyrolactone and α-acetoxymethyl-γ-butyrolactone

This invention pertains to a process for making α-methylene-γ-butyrolactone by acid-catalyzed rearrangement of tetrahydro-3-furoic acid. In a further embodiment, when tetrahydro-3-furoic acid is treated with acetic anhydride and an acid catalyst, α-acetoxymethyl-γ-butyrolactone is produced in high yield. Under basic conditions, α-acetoxymethyl-γ-butyrolactone can readily formα-methylene-γ-butyrolactone by the elimination of acetic acid. These reactions provide α-methylene-γ-butyrolactone by novel routes which do not require butyrolactone or formaldehyde.

Novel selective PDE4 inhibitors. 1. Synthesis, structure-activity relationships, and molecular modeling of 4-(3,4-dimethoxyphenyl)-2H-phthalazin-1-ones and analogues

A number of 6-(3,4-dimethoxyphenyl)-4,5-dihydro-2H-pyridazin-3-ones and a novel series of 4-(3,4-dimethoxyphenyl)-2H-phthalazin-1-ones were prepared and tested on the cGMP-inhibited phosphodiesterase (PDE3) and cAMP-specific phosphodiesterase (PDE4) enzymes. All tested compounds were found to specifically inhibit PDE4 except for pyridazinone 3b, which showed moderate PDE4 (pIC50 = 6.5) as well as PDE3 (pIC50 = 6.6) inhibitory activity. In both the pyridazinone and phthlazinone series it was found that N-substitution is beneficial for PDE4 inhibition, whereas in the pyridazinone series it also accounts for PDE4 selectivity. In the phthalazinone series, the cis-4a,5,6,7,8,8a-hexahydrophthalazinones and their corresponding 4a,5,8,8a-tetrahydro analogues showed potent PDE4 inhibitory potency (10/11c,d: pIC50 = 7.6-8.4). A molecular modeling study revealed that the cis-fused cyclohexa(e)ne rings occupy a region in space different from that occupied by the other fused (un)saturated hydrocarbon rings applied; we therefore assume that the steric interactions of these rings with the binding site play an important role in enzyme inhibition.

SUBSTITUTED CYCLOALKANECARBOXYLIC ACID DERIVATIVES AS MATRIX METALLOPROTEASE INHIBITORS

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula STR1 wherein each T is a substituent g roup; x is 0, 1, or 2; the group D represents STR2 the subscript "e" is 2 or 3; the group R 14 represents a variety of possible substituent groups of the cycloalkyl ring between D and G; the subscript "k" is 0-2; and the group G represents M, STR3 in which M represents--CO 2 H,--CON(R 11) 2, or--CO 2 R 12 ; and R 13 represents any of the side chains of the 19 noncyclic occurring amino acids. "

Synthesis of Small-Medium Ring Thioanhydrides

Reaction of five-membered ring anhydrides with sodium sulfide has previously been employed for synthesis of the corresponding thioanhydrides in low yields.Re-examination of the stoichiometry reveals reaction of cyclic anhydride with sodium sulfide (2:1 respectively), affords the thioanhydride accompanied by the corresponding dicarboxylate in a 1:1 molar ratio.The mechanistic pathway for this reaction has also been elucidated.Optimization of reaction conditions has resulted in the synthesis of a variety of four to seven-membered ring thioanhydride in yields approaching theoretical.