37027-56-8Relevant articles and documents
Novel lipid-mimetic prodrugs delivering active compounds to adipose tissue
Mattarei, Andrea,Rossa, Andrea,Bombardelli, Veronica,Azzolini, Michele,La Spina, Martina,Paradisi, Cristina,Zoratti, Mario,Biasutto, Lucia
, p. 77 - 88 (2017)
Obesity and associated pathologies are a dramatically growing problem. New therapies to prevent and/or cure them are strongly needed. Adipose tissue is a logical target for pharmacological intervention, since it is now recognized to exert an important endocrine function, secreting a variety of adipokines affecting, for example, adiposity and insulin resistance. This proof of principle work focuses on the development of novel lipid-mimetic prodrugs reaching fat deposits by the same lymphatic absorption route followed by dietary triglycerides. Pterostilbene, a natural phenolic compound with potential anti-obesity effects, was used as model “cargo”, attached via a carbamate group to an ω-aminodecanoate chain linked to either position 1 or position 2 of the glycerol moiety of synthetic triglycerides. The prodrugs underwent position-selective hydrolysis when challenged with pancreatic lipases in vitro. Pterostilbene-containing triglycerides as well as pterostilbene and its metabolites were present in the adipose tissue of mice fed an obesogenic diet containing one or the other of the derivatives. For the first time this approach is used to deliver an obesity antagonist to the adipose tissue. The results demonstrate the feasibility of delivering active compounds to adipose tissue by reversibly incorporating them into triglyceride-mimetic structures. Upon release in the target site these compounds are expected to exert their pharmacological activity precisely where needed.
CATALYTIC CARBOXYLATION OF ACTIVATED ALKANES AND/OR OLEFINS
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Page/Page column 65; 66; 67, (2018/02/28)
The present invention relates to a method of reacting starting materials with an activating group, namely alkanes carrying a leaving group and/or olefins, with carbon dioxide under transition metal catalysis to give carboxyl group-containing products. It is a special feature of the method of the present invention that the carboxylation predominantly takes place at a preferred position of the molecule irrespective of the position of the activating group. The carboxylation position is either an aliphatic terminus of the molecule or it is a carbon atom adjacent to a carbon carrying an electron withdrawing group. The course of the reaction can be controlled by appropriately choosing the reaction conditions to yield the desired regioisomer.
Remote carboxylation of halogenated aliphatic hydrocarbons with carbon dioxide
Juliá-Hernández, Francisco,Moragas, Toni,Cornella, Josep,Martin, Ruben
, p. 84 - 88 (2017/05/12)
Catalytic carbon-carbon bond formation has enabled the streamlining of synthetic routes when assembling complex molecules. It is particularly important when incorporating saturated hydrocarbons, which are common motifs in petrochemicals and biologically relevant molecules. However, cross-coupling methods that involve alkyl electrophiles result in catalytic bond formation only at specific and previously functionalized sites. Here we describe a catalytic method that is capable of promoting carboxylation reactions at remote and unfunctionalized aliphatic sites with carbon dioxide at atmospheric pressure. The reaction occurs via selective migration of the catalyst along the hydrocarbon side-chain with excellent regio- and chemoselectivity, representing a remarkable reactivity relay when compared with classical cross-coupling reactions. Our results demonstrate that site-selectivity can be switched and controlled, enabling the functionalization of less-reactive positions in the presence of a priori more reactive ones. Furthermore, we show that raw materials obtained in bulk from petroleum processing, such as alkanes and unrefined mixtures of olefins, can be used as substrates. This offers an opportunity to integrate a catalytic platform en route to valuable fatty acids by transforming petroleum-derived feedstocks directly.
