Stereochemistry and biological activity of chlorinated lipids: a study of danicalipin A and selected diastereomers

Abstract

Impact of configuration and conformation of selected (+)-danicalipin A diastereomers on biological activity.

Synthesis of Vicinal Dichlorides via Activation of Aliphatic Terminal Epoxides with Triphosgene and Pyridine

“…As a result of the two adjoining electrophilic carbons, epoxides could theoretically be subjected to double nucleophilic displacement by two chloride ions. There are a few reports demonstrating that treatment of epoxide with Appel-type activation conditions, i.e., triphenylphosphine and a source of electrophilic chlorine, readily furnished the corresponding vicinal dichloride. Nonetheless, similar to any synthetic transformations that rely on nucleophilic activation of reactive intermediates using a stoichiometric amount of triphenylphosphine, these established chlorination conditions suffered from disadvantages from both atom economical and operational perspectives, as it is necessary and often difficult to purify the corresponding alkyl chloride from the leftover reagents and byproducts, especially given the potential instability of organochlorines under column chromatographic separation.…”

Chlorosulfolipid (Danicalipin A) Membrane Structure: Hybrid Molecular Dynamics Simulation Studies

“…We observed that Danicalipin A lipids form a stable monolayer membrane structure wherein each lipid adopts a bent geometry consistent with the prediction reported by Carreira's group. 12 The corresponding atomistic MD simulation confirms that the monolayer membrane with the bent geometry indeed plays a role as a biological membrane by prohibiting water from passing through it up to as high as 313 K. In addition, there exists a gel-to-liquid-crystalline phase transition around 298 K similar to conventional biological membranes. We also showed that the Dancalipin A lipids are closely packed in an up-anddown manner, which leads to strong resistance against area compression and slow diffusion compared to conventional biological bilayer membranes.…”

“…1,11 Carreira's group have recently reported the connection between stereochemistry and the biological activity of chlorinated lipids using Danicalipin A (Figure 1) and its diastereomers. 12 They observed that the bent configuration of Danicalipin A has distinct membrane permeability and cytotoxicity compared to linear or zigzag shaped diastereomers; further, they speculated that this particular shape of Danicalipin A may have effects on the motility in the flagellum of O. danica by introducing a kink in the lipid chain, which is analogous to cis-unsaturation in fatty acids.…”

“…Thus far, structural information about CSLs, which can reveal the significant roles CSLs would play in biological systems, is lacking. Haines group reported that CSLs are constituents of the flagellar cell membranes instead of phospholipids; however, there are only few studies that focus on how CSLs are arranged in the membrane. , Carreira’s group have recently reported the connection between stereochemistry and the biological activity of chlorinated lipids using Danicalipin A (Figure ) and its diastereomers . They observed that the bent configuration of Danicalipin A has distinct membrane permeability and cytotoxicity compared to linear or zigzag shaped diastereomers; further, they speculated that this particular shape of Danicalipin A may have effects on the motility in the flagellum of O. danica by introducing a kink in the lipid chain, which is analogous to cis-unsaturation in fatty acids.…”

1,10-Secoguaianolides from Artemisia austro-yunnanensis and Their Anti-Inflammatory Effects

“…Further, each tested compound displayed different potency on each inflammatory factor due to its structural difference, although they all possess same basic skeleton. It indicated that 3D-strcuture is very important in the bioactivity [ 45 , 46 , 47 , 48 , 49 ]. Taken together from PCA, the structural similarity between 2 and 3 is relatively higher than that of the others, and they displayed better effects against IL-1 ß , IL-6 and PGE2 than the others.…”