99557-34-3

Upstream product

• 23304-25-8 p-methoxyphenyldiazomethane 
• 91-56-5 indole-2,3-dione 
• 53825-23-3 4'-Methoxydehydrocyclopeptin 
• 150256-42-1 2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)benzoic acid 
• 38957-44-7 2-(4-methoxybenzene-sulfonylamino)benzoic acid 
• 36192-61-7 2-amino-4'-methoxybenzophenone 
• 123-11-5 4-methoxy-benzaldehyde 
• 3415-35-8 4-methyl-3H-1,4-benzodiazepine-2,5-(1H,4H)-dione 
• 118-48-9 isatoic anhydride 
• 52939-33-0 (S)-N-methyl-4-methoxyphenylalanine 

Relevant academic research and scientific papers

Diastereomeric quinolinone alkaloids from the marine-derived fungus Penicillium janczewskii

From Penicillium janczewskii, obtained from a marine sample, two new diastereomeric quinolinones, 3S*,4R*-dihydroxy-4-(4′- methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (1) and 3R*,4R*- dihydroxy-4-(4′-methoxyphenyl)-3,4-dihydro-2(Lif)-quinolinone (2), wer

Harnessing the Substrate Promiscuity of Dioxygenase AsqJ and Developing Efficient Chemoenzymatic Synthesis for Quinolones

Nature has developed complexity-generating reactions within natural product biosynthetic pathways. However, direct utilization of these pathways to prepare compound libraries remains challenging because of limited substrate scopes, involvement of multiple-step reactions, and moderate robustness of these sophisticated enzymatic transformations. Synthetic chemistry offers an alternative approach to prepare natural product analogues. However, because of complex and diverse functional groups appended on the targeted molecules, dedicated design and development of synthetic strategies are typically required. Herein, by leveraging the power of chemoenzymatic synthesis, we report an approach to bridge the gap between biological and synthetic strategies in the preparation of quinolone alkaloid analogues. Leading byin silicoanalysis, the predicted substrate analogues were chemically synthesized. The AsqJ-catalyzed asymmetric epoxidation of these substrate analogues was followed by a Lewis acid-triggered ring contraction to complete the viridicatin formation. We evaluated the robustness of this method in gram-scale reactions. Lastly, through chemoenzymatic cascades, a library of quinolone alkaloids is effectively prepared.

Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones

Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.

Deoxygenative Arylation of Carboxylic Acids by Aryl Migration

An unprecedented deoxygenative arylation of aromatic carboxylic acids has been achieved, allowing the construction of an enhanced library of unsymmetrical diaryl ketones. The synergistic photoredox catalysis and phosphoranyl radical chemistry allows for precise cleavage of a stronger C?O bond and formation of a weaker C?C bond by 1,5-aryl migration under mild reaction conditions. This new protocol is independent of substrate redox-potential, electronic, and substituent effects. It affords a general and promising access to 60 examples of synthetically versatile o-amino and o-hydroxy diaryl ketones under redox-neutral conditions. Furthermore, it also brings one concise route to the total synthesis of quinolone alkaloid, (±)-yaequinolone A2, and a viridicatin derivative in satisfying yields.

Regioselective Ring Expansion of Isatins with in Situ Generated α-Aryldiazomethanes: Direct Access to Viridicatin Alkaloids

A novel efficient one-pot regioselective ring-expansion reaction of isatins with in situ generated α-aryl/heteroaryldiazomethanes for the construction of viridicatin alkaloids has been described under metal-free conditions. The utility of this protocol is further demonstrated in the synthesis of naturally occurring viridicatin, viridicatol, and substituted 3-O-methyl viridicatin and their scale up.

Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis

Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The FeII/α-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4′-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.