The synthesis of marine nucleosides trachycladines A and B and two nucleoside analogues was accomplished following a versatile and high‐yielding scheme starting from D‐ribose. The key step involved a regio‐ and stereoselective direct Vorbrüggen glycosylation reaction between the appropriate nucleobase and a common intermediate, 2‐C‐methyl‐D‐5‐deoxyribofuranose triacetate.

Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are Δ 12 -prostaglandin J 2 (Δ 12 -PGJ 2 ) and Δ 12 -prostaglandin J 3 (Δ 12 -PGJ 3 ), whose unusual structural motifs and potent cytotoxicities present unique opportunities for chemical and biological investigations. Herein, we report a short olefin-metathesis-based total synthesis of Δ 12 -PGJ 2 and its application to the construction of a series of designed analogues possessing monomeric, dimeric, trimeric, and tetrameric macrocyclic lactones consisting of units of this prostaglandin. Biological evaluation of these analogues led to interesting structure−activity relationships and trends and the discovery of a number of more potent antitumor agents than their parent naturally occurring molecules.

The total synthesis of cytotoxic meroditerpenoid naphthoquinone derivative chabrolonaphthoquinone B (1) in an enantiospecific manner is divulged using a chiral pool approach. The key step of our synthetic route is a modified Julia olefination between a sulfone-bearing aliphatic fragment and a Diels–Alder-derived aromatic aldehyde, leading to the stereoselective construction of the E-trisubstituted double bond.

A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure–activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as “synthetic nucleases”, independently of oxygen and pH. Calf thymus–DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating DNA-photocleavers, and are proposed as new leads for “on demand” biotechnological applications in drug discovery and medicine.

The synthesis of four new analogues of marine nucleoside trachycladine A was accomplished by direct regio- and stereoselective Vorbrüggen glycosylations of 2,6-dichloropurine and 2-chloropurine with a d-ribose-derived chiron. Naturally occurring trachycladines A and B and a series of analogues were examined for their cytotoxic activity against a number of cancer cell lines (glioblastoma, lung, and cervical cancer). Parent trachycladine A and two analogues (the diacetate of the 2,6-dichloropurine derivative and N-cyclopropyl trachycladine A) resulted in a significant decrease in cell viability, with the latter exhibiting a stronger effect. The same compounds enhanced the cytotoxic effect of docetaxel in lung cancer cell lines, whereas additional experiments revealed that their mode of action relies on mitotic catastrophe rather than DNA damage. Moreover, their activity as autophagic flux blockers was postulated.