A convergent strategy for the pamamycin macrodiolides:Total synthesis of pamamycin-607, pamamycin-593, and pamamycin-621D precursors

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First total synthesis of pamamycin-621D

Aim and Objective: The objective of our work was to synthesize and fully characterize Pamamycin- 621D, one of the less abundant members of a large family of macrodiolides with antimycobacterial properties, which had never been synthesized before. Furthermore, we also wished to improve our general strategy by using a new unsaturated precursor. Materials and Method: A new unsaturated ethylketone precursor was prepared using alkene cross metathesis, and a convergent and flexible strategy based on a key diastereoselective aldol addition was implemented to afford pamamycin-621D in 12 steps from that precursor. Results: Pamamycin-621D has been obtained and fully characterized for the first time. The structure of pamamycin-621D was confirmed by HRMS and comparison of 1H-NMR spectra with the natural pamamycin- 621D. Both optical rotation and 13C-NMR had not been published previously due to lack of material, and the latter are reported here for the first time. Given the scarce characterization available previously, our synthesis also gives additional support to the initial structural assignment of pamamycin-621D. A significant improvement of the key aldol addition via the use of a new unsaturated precursor is also reported. Conclusion: The work described above constitutes the first total synthesis of pamamycin-621D and has enabled us to fully characterize this scarcely available natural product. More importantly, this work highlights the fact that our synthetic approach provides ready access to various members of the pamamycin family, allowing possible studies on structure-activity relationships and mode of action of even the least abundant of these natural products. The synthesis of other pamamycin congeners and biological investigations will be published in due course. </jats:sec

Synthesis of Cr(III) Salen Complexes as Supramolecular Catalytic Systems for Ring-Opening Reactions of Epoxides

The synthesis of two conformationally restricted Cr(III) salen complexes, 2 and 3, is described. Together, they constitute a supramolecular hydrogen-bonding catalytic system for the recently reported asymmetric ring-opening reactions of epoxides by a dynamic supramolecular catalyst. The synthesis involves state-of-the art transformations in frontline synthetic chemistry applied to heterocyclic chemistry. Hence, palladium-catalyzed reactions were employed, including carbonylative annelation and Suzuki cross-coupling reactions, for the formation of one of the heterocyclic rings (quinolone) and the functionalization of the formed rings. For the construction of the second heterocyclic ring (isoquinolone), a Curtius rearrangement was employed. The corresponding salen ligands were then prepared by Schiff-base reactions, yielding the final complexes after metal insertion. For reference purposes the less conformationally restricted Cr(III) complexes 4 and 5 were also synthesized

Synthesis and photophysical properties of C3-symmetric tris(pyridyl)truxene scaffolds of Ru(II) and Re(I)

Facial Ru(II)- and Re(I)-complexes of a novel face-capping tris(pyridyl)truxene ligand were synthesised and characterised by various analytical techniques including single crystal XRD. The Ru(II) complex exhibits unusual green phosphorescence with a long excited-state lifetime