Organometallic modification confers oligonucleotides new functionalities.

To improve their properties or to introduce entirely new functionalities, the intriguing scaffolds of nucleic acids have been decorated with various modifications, most recently also organometallic ones. While challenging to introduce, organometallic modifications offer the potential of expanding the field of application of metal-dependent functionalities to metal-deficient conditions, notably those of biological media. So far, organometallic moieties have been utilized as probes, labels and catalysts. This Feature Article summarizes recent efforts and predicts likely future developments in each of these lines of research.

An accelerated Rauhut-Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies.

The total synthesis of racemic incarvilleatone has been achieved by utilizing unexplored accelerated Rauhut-Currier (RC) dimerization. The other key steps of the synthesis are oxa-Michael and aldol reactions in a tandem sequence. Racemic incarvilleatone was separated by chiral HPLC and the configuration of each enantiomer was determined by single-crystal X-ray analysis. In addition, a one-pot synthesis of (±)-incarviditone has been achieved from rac-rengyolone by using KHMDS as a base. We have also assessed the anticancer activity of all the synthesized compounds in breast cancer cells nonetheless, they exhibited very limited growth suppression activity.

Oligonucleotides Featuring a Covalently Mercurated 6-Phenylcarbazole Residue as High-Affinity Hybridization Probes for Thiopyrimidine-Containing Sequences.

Short oligonucleotides incorporating either 1-mercuri-6-phenylcarbazole, 8-mercuri-6-phenylcarbazole, or 1,8-dimercuri-6-phenylcarbazole C-nucleoside in the middle of the chain have been synthesized and studied for their potential as hybridization probes for sequences containing thiopyrimidine nucleobases. All of these oligonucleotides formed very stable duplexes with complementary sequences pairing the organometallic moiety with either 2- or 4-thiothymine. The isomeric monomercurated oligonucleotides were also able to discriminate between 2- and 4-thiothymine based on the different melting temperatures of the respective duplexes. DFT-optimized structures of the most stable mononuclear HgII -mediated base pairs featured a coordinated covalent bond between HgII and either S2 or S4 and a hydrogen bond between the carbazole nitrogen and N3. The dinuclear HgII -mediated base pairs, in turn, were geometrically very similar to the one previously reported to form between 1,8-dimercuri-6-phenylcarbazole and thymine and had one HgII ion coordinated to a thio and the other one to an oxo substituent.

Synthesis of artemisinic acid derived glycoconjugates and their anticancer studies.

Glycoconjugates, due to their diverse functions, are widely regarded as biologically important molecules. Artemisinic acid 1 occurs naturally in the plant Artemisia annua and is considered to be the biogenetic precursor of the antimalarial drug, artemisinin 2. We report herein the design and synthesis of diverse artemisinic acid derived glycoconjugates. We have synthesized 12-O-artemisinic acid-glycoconjugates (7a-k) and 12-N-artemisinic acid-glycoconjugates (8a-k) by utilizing Cu(i)-catalyzed azide-alkyne cycloaddition reactions (Click chemistry) with various synthesized sugar azides (6a-k) in good to excellent yields along with two fluorescently labeled compounds, 12-O-artemisinic acid-glycoconjugate 11 and 12-N-artemisinic acid-glycoconjugate 12, to investigate the mode of action of these compounds in biological systems. All the synthesized artemisinic acid glycoconjugates were assayed for their efficacy against the MCF7 cell line. Our anticancer studies indicated that all the synthesized compounds inhibited the growth of MCF7 cells in a dose dependent manner, barring compounds 4 and 7d. However, these compounds exhibit moderate cytotoxicity, as is evident from their IC50 values.

Unusual Epimerization in Styryllactones: Synthesis of (-)-5-Hydroxygoniothalamin, (-)-5-Acetylgoniothalamin, and O-TBS-Goniopypyrone.

(-)-5-Hydroxygoniothalamin, (-)-5-acetylgoniothalamin, and (+)-5-hydroxygoniothalamin, isolated from the Goniothalamus genus, are synthesized from triacetyl-O-d-glucal by employing the Ferrier reaction, Mitsunobu reaction, and Jones oxidation as key steps. The synthetic procedure also yields the epimers of (-)-5-hydroxygoniothalamin and (+)-5-hydroxygoniothalamin employing acid-mediated transition-metal-free epimerization at C-5 of styryllactones. Further studies reveal that the epimerization is facilitated by the phenyl group present on the styryllactones. Also, depending on the dihydroxylation reaction conditions, various analogues of saturated styryllactones are synthesized utilizing oxa-Michael reaction conditions.

Biomimetic Total Synthesis of Angiopterlactone B and Other Potential Natural Products.

A one-pot biomimetic synthesis of (-)-angiopterlactone B and its enantiomer (+)-angiopterlactone B has been accomplished via TBAF-catalyzed tandem ring contraction followed by oxa-Michael/Michael addition sequence. Comparison of specific optical rotations, absolute configurations, and CD spectra of natural, synthesized (-)-angiopterlactone B and (+)-angiopterlactone B unequivocally proves that the isolated angiopterlactone B must be levorotatory. Synthesis of hitherto undiscovered natural products 18 and 20 and analogues of angiopterlactone B demonstrate the versatility of this method.