65100-24-5

Upstream product

• 100-39-0 benzyl bromide 
• 100-51-6 benzyl alcohol 
• 15014-25-2 malonic acid dibenzyl ester 

Downstream Products

• 409109-82-6 anilino-malonic acid dibenzyl ester 
• 380413-19-4 2-((1R,5R)-7-Oxo-3-phenoxymethyl-4-thia-2,6-diaza-bicyclo[3.2.0]hept-2-en-6-yl)-malonic acid dibenzyl ester 
• 408537-95-1 4-oxo-1-phenyl-azetidine-2,2-dicarboxylic acid dibenzyl ester 
• 1239504-94-9 benzyl 4-hydroxy-2-(6-methylpyrazolo[5,1-b][1,3]thiazol-7-yl)-1,3-thiazole-5-carboxylate hydrobromide 
• 936567-85-0 2-(1-benzyl-2-methyl-1H-indol-4-yloxy)-malonic acid dibenzyl ester 
• 927678-38-4 dibenzyl [(4-methoxyphenyl)amino]malonate 
• 1089672-00-3 dibenzyl 2-(4-methoxyphenyl)cyclopropane-1,1-dicarboxylate 

Relevant academic research and scientific papers

A Total Synthesis of Salinosporamide A

Salinosporamide A is a β-lactone proteasome inhibitor currently in clinical trials for the treatment of multiple-myeloma. Herein we report a short synthesis of this small, highly functionalized, biologically important natural product that uses an oxidative radical cyclization as a key step and allows for the preparation of gram quantities of advanced synthetic intermediates.

Synthesis of spiro[2.5]octa-4,7-dien-6-one with consecutive quaternary centers via 1,6-conjugate addition induced dearomatization of para-quinone methides

An efficient one-pot approach for the synthesis of spiro[2.5]octa-4,7-dien-6-ones by employing para-quinone methides has been developed. The reaction proceeded smoothly in high yields under mild conditions without the use of metals. Moreover, all products obtained herein contained two or three consecutive quaternary centers.

HETEROARYLS AND THEIR USE AS PI3K INHIBITORS

This invention provides compounds of formula (IA) or (IB): wherein R1, R2, G1 and HY are as described in the specification. The compounds are inhibitors of PI3K and/or mTor and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.

PHOSPHOLIPASE INHIBITORS, INCLUDING MULTI-VALENT PHOSPHOLIPASE INHIBITORS, AND USE THEREOF, INCLUDING AS LUMEN-LOCALIZED PHOSPHOLIPASE INHIBITORS

The present invention provides methods and compositions for the treatment of phospholipase-related conditions. In particular, the invention provides a method of treating insulin-related, weight-related conditions and/or cholesterol-related conditions in an animal subject. The method generally involves the administration of a non-absorbed and/or effluxed phospholipase A2 inhibitor that is localized in a gastrointestinal lumen.

INDOLE COMPOUNDS HAVING C4-ACIDIC SUBSTITUENTS AND USE THEREOF AS PHOSPHOLIPASE-A2 INHIBITORS

Indole and indole-related compounds, compositions and methods are disclosed. The compounds of the invention are useful as phospholipase inhibitors. The compounds and compositions of the invention are useful for treatment of phospholipase-related conditions, such as insulin-related, weight-related and/or cholesterol-related conditions in an animal subject.

Multivalent indole compounds and use thereof as phospholipase-A2 inhibitors

Indole and indole-related compounds, compositions and methods are disclosed. The compounds of the invention are useful as phospholipase inhibitors. The compounds and compositions of the invention are useful for treatment of phospholipase-related conditions, such as insulin-related, weight-related and/or cholesterol-related conditions in an animal subject.

Synthesis of thienamycin-like 2-iso-oxacephems with optional stereochemistry

All four trans-stereoisomers of 7-(1-hydroxyethyl)-2-iso-oxacephem-4-carboxylic acids, which are the 2-iso-oxacephem analogues of Thienamycin, have been synthesized. (αR,6R,7R)- and (αS,6S,7S)-7-(1-hydroxyethyl)-3-methyl-2-iso-oxacephem-4-carboxylic acids have been prepared starting from l- and d-threonine, the configuration at the α-position was inverted by using Mitsunobu reactions providing the (αS,6R,7R)- and (αR,6S,7S)-diastereomers of the compounds above. A synthetic route to the cis-annelated analogues was also worked out.

Synthesis and decarboxylation of Δ2-cephem-4,4-dicarboxylic acids

Penicillin V was converted in 14 steps into Δ2-cephems having hydrogen at C-3, hydrogen or methyl at C-2, and two methoxycarbonyl, two benzyloxycarbonyl, or one methoxycarbonyl and one benzyloxycarbonyl substituent at C-4. Deprotection of these Δ2-cephem-4,4-dicarboxylic acid esters by alkaline hydrolysis (in the case of methyl esters) or hydrogenolysis (in the case of benzyl esters) led in all cases to rapid decarboxylation of the Δ2-cephem-4,4-dicarboxylic acid or Δ2-cephem-4,4-dicarboxylic acid monoester. With hydrogen at C-2, hydrolysis of the dimethyl ester with 1 equiv of base produced a Δ2-cephem. With 2 equiv of base, and with all compounds having methyl at C-2, hydrolysis or hydrogenolysis afforded 4α-substituted-Δ2-cephems. In contrast, simpler benzyl or methyl acetamidomalonates could be deprotected without difficulty to afford stable malonic acids. Reasons for the differences in ease of decarboxylation were examined using semiempirical (AM1) and ab initio (3-21G) molecular orbital calculations. The decarboxylation barriers of unionized cephem or acetamido malonic acids were found to be high (35-40 kcal mol-1). Although the monoanion of acetamidomalonic acid retained a high barrier, the epimeric monoanions of a Δ2-cephem malonic acid decarboxylated with barriers of only 2 kcal mol-1.

A GENERAL ROUTE TOWARD 2-OXO-, 2-THIOXO- AND 2-IMINOPENAMS AND THEIR CONVERSION INTO 2-ALKOXY-, 2-ALKYLTHIO- AND 2-AMINOPENEMS

A convenient methodology is described which allows the preparation of 2-oxo-, 2-thioxo- and 2-iminopenams from a single precursor readily prepared from penicillin G.These penams have been converted into the corresponding 2-heterosubstituted penems.