The Versatile and Strategic O-Carbamate Directed Metalation Group in the Synthesis of Aromatic Molecules: An Update.

The aryl O-carbamate (ArOAm) group is among the strongest of the directed metalation groups (DMGs) in directed ortho metalation (DoM) chemistry, especially in the form Ar-OCONEt2. Since the last comprehensive review of metalation chemistry involving ArOAms (published more than 30 years ago), the field has expanded significantly. For example, it now encompasses new substrates, solvent systems, and metalating agents, while conditions have been developed enabling metalation of ArOAm to be conducted in a green and sustainable manner. The ArOAm group has also proven to be effective in the anionic ortho-Fries (AoF) rearrangement, Directed remote metalation (DreM), iterative DoM sequences, and DoM-halogen dance (HalD) synthetic strategies and has been transformed into a diverse range of functionalities and coupled with various groups through a range of cross-coupling (CC) strategies. Of ultimate value, the ArOAm group has demonstrated utility in the synthesis of a diverse range of bioactive and polycyclic aromatic compounds for various applications.

Mixed micellar nanoparticle of amphotericin B and poly styrene-block-poly ethylene oxide reduces nephrotoxicity but retains antifungal activity.

Mixed micellar nanoparticle consisting of amphotericin B (AmB) and poly styrene-block-poly ethylene oxide (PS-block-PEO) was prepared by high pressure homogenizer. Nephrotoxicity of the nanoparticle was investigated along with antifungal activity and self-aggregation status of the drug in the nanoparticle. Nephrotoxicity was markedly reduced when AmB was intravenously administered to rats as mixed micellar nanoparticle with PS-block-PEO in terms of transmission electron microscopy of tubular cells and creatinine clearance. Antifungal activity of AmB was not altered when the drug was in the form of mixed micellar nanoparticle compared to both conventional formulation and AmB micelle treated by same procedure without PS-block-PEO. Self-aggregation status of AmB molecules revealed monomeric in the mixed micellar nanoparticle with PS-block-PEO up to the therapeutic level of the drug (1-3 mM). The reduced nephrotoxicity of AmB in mixed micellar nanoparticle may be associated with the existence of the drug as monomeric form in the nanoparticle. Based on our result, formulation of AmB as mixed micellar nanoparticle with PS-block-PEO may be a promising alternative for the treatment of fungal diseases in patients who are at risk of renal dysfunction.

Synthesis of decapeptide of L-aspartic acid and benzyl-L-aspartic acid by solid phase peptide synthesis.

Polyene macrolide amphotericin B (AmB) is the drug of choice for the treatment of disseminated fungal infections. However, because of its pronounced side effects, the drug has limited applicability. There are few interesting reports, which state that co-administration of the drug with homo-peptide of polyaspartic acid reduces the side effects of the drug. In our present study, an approach has been made to systematically synthesize low molecular weight heteropeptides consisting of L-aspartic acid and its derivative. It was hypothesized that such heteropeptides will reduce the toxic side effects of the drug by facile hydrophobic binding between the polymer and the drug. We have employed the strategy of solid phase peptide synthesis (SPPS) to synthesize low molecular weight hetero-peptides by using L-aspartic acid and benzyl-L-aspartic acid to induce the hydrophobic binding between the peptide and the drug. In future, the proposed methodology can be employed to tailor other polypeptides substituted with benzyl groups to reduce the nephrotoxicity of AmB.