Synthesis of bioconjugate sesterterpenoids with phospholipids and polyunsaturated fatty acids

A series of sesterterpenoid bioconjugates with phospholipids and polyunsaturated fatty acids (PUFAs) have been synthesized for biological activity testing as antiproliferative agents in several cancer cell lines. Different substitution analogues of the original lipidic ether edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) are obtained varying the sesterterpenoid in position 1 or 2 of the glycerol or a phosphocholine or PUFA unit in position 3. Simple bioconjugates of sesterterpenoids and eicosapentaenoic acid (EPA) have been obtained too. All synthetic derivatives were tested against the human tumour cell lines HeLa (cervix) and MCF-7 (breast). Some compounds showed good IC50 (0.3 and 0.2 μM) values against these cell lines.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2011-30518 and SAF2014-59716-R). Junta de Castilla y León BIO/SA59/15.Peer reviewe

Halimanes and cancer: ent-halimic acid as a starting material for the synthesis of antitumor drugs

The development of new anti-cancer agents is an urgent necessity nowadays, as it is one of the major causes of mortality worldwide. Many drugs currently used are derived from natural products. Halimanes are a class of bicyclic diterpenoids present in various plants and microorganisms. Many of them exhibit biological activities such as antitumor, antimicrobial, or anti-inflammatory. Among them, ent-halimic acid is an easily accessible compound, in large quantities, from the ethyl acetate extract of the plant Halimium viscosum, and it has been used as a starting material in a number of bioactive molecules. In this work, we review all the natural halimanes with antitumor and related activities until date as well as the synthesis of antitumor compounds using ent-halimic acid as a starting material

Organocatalyzed Synthesis of [3.2.1] Bicyclooctanes

Organocatalysis constitutes one of the main research areas in organic chemistry from the last two decades. This chemistry has been applied to the synthesis of many natural products and structures in a manner that reduces the residues and so the ecological impact. In this review, we consider the work that has been done for the synthesis of bicyclo[3.2.1]octane framework. This structure is present in many natural products with very important biological activities

Antibacterial Natural Halimanes: Potential Source of Novel Antibiofilm Agents

The development of new agents against bacteria is an urgent necessity for human beings. The structured colony of bacterial cells, called the biofilm, is used to defend themselves from biocide attacks. For this reason, it is necessary to know their structures, develop new agents to eliminate them and to develop new procedures that allow an early diagnosis, by using biomarkers. Among natural products, some derivatives of diterpenes with halimane skeleton show antibacterial activity. Some halimanes have been isolated from marine organisms, structurally related with halimanes isolated from Mycobacterium tuberculosis. These halimanes are being evaluated as virulence factors and as tuberculosis biomarkers, this disease being one of the major causes of mortality and morbidity. In this work, the antibacterial halimanes will be reviewed, with their structural characteristics, activities, sources and the synthesis known until now

Synthesis of Bioconjugate Sesterterpenoids with Phospholipids and Polyunsaturated Fatty Acids

A series of sesterterpenoid bioconjugates with phospholipids and polyunsaturated fatty acids (PUFAs) have been synthesized for biological activity testing as antiproliferative agents in several cancer cell lines. Different substitution analogues of the original lipidic ether edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) are obtained varying the sesterterpenoid in position 1 or 2 of the glycerol or a phosphocholine or PUFA unit in position 3. Simple bioconjugates of sesterterpenoids and eicosapentaenoic acid (EPA) have been obtained too. All synthetic derivatives were tested against the human tumour cell lines HeLa (cervix) and MCF-7 (breast). Some compounds showed good IC50 (0.3 and 0.2 μM) values against these cell lines

Diastereoselective Synthesis of 7,8-Carvone Epoxides

The synthesis of the two 7,8-epoxides of carvone has been attained using organocatalysis in a two-step synthetic route through a bromoester intermediate. Among the different reaction conditions tested for the bromination reaction, moderate yields and diastereoselection are achieved using proline, quinidine, and diphenylprolinol, yielding the corresponding bromoesters that were transformed separately into their epoxides, obtaining the enantiopure products

Diastereoselective synthesis of chiral 1,3-cyclohexadienals

<div><p>A novel approach to the production of chiral 1,3-cyclohexadienals has been developed. The organocatalysed asymmetric reaction of different β-disubstituted-α,β-unsaturated aldehydes with a chiral α,β-unsaturated aldehyde in the presence of a Jørgensen-Hayashi organocatalyst provides easy and stereocontrolled access to the cyclohexadienal backbone. This method allows for the synthesis of potential photoprotective chiral 1,3-cyclohexadienals and extra extended conjugation compounds in a simple manner.</p></div

Experimental optimization of synthesis of chiral cyclohexadienals (4a, 4b) from citral (1) and α,β-unsaturated aldehyde 2.

<p>Experimental optimization of synthesis of chiral cyclohexadienals (4a, 4b) from citral (1) and α,β-unsaturated aldehyde 2.</p

General reaction to obtain chiral cyclohexadienals.

<p>General reaction to obtain chiral cyclohexadienals.</p

Synthesis of different chiral cyclohexadienals aromatic and non-aromatic compounds.

<p>Synthesis of different chiral cyclohexadienals aromatic and non-aromatic compounds.</p