An Approach to <i>seco</i>-Prezizaane Sesquiterpenoids: Enantioselective Total Synthesis of (+)‑1<i>S</i>‑Minwanenone

A strategy of general applicability toward <i>seco</i>-prezizaane sesquiterpenes, from a chiral, tricyclic synthon, readily available via an enzymatic resolution step from the Diels–Alder adduct of cyclopentadiene and <i>p</i>-benzoquinone, has been devised. Our approach enables harnessing of the stereochemical proclivities of the norbornyl system to install the desired stereochemistry at the key stereogenic centers. Recourse to an interesting stratagem to realign a stereochemical divergence into stereoreconvergence forms the cornerstone of our successful approach. The first total synthesis of (+)-1<i>S</i>-minwanenone, a prototypical member of <i>seco</i>-prezizaane subclass, has been accomplished

Synthesis and Antiribosomal Activities of 4′‑<i>O</i>‑, 6′‑<i>O</i>‑, 4″‑<i>O</i>‑, 4′,6′‑<i>O</i>- and 4″,6″‑<i>O</i>-Derivatives in the Kanamycin Series Indicate Differing Target Selectivity Patterns between the 4,5- and 4,6-Series of Disubstituted 2‑Deoxystreptamine Aminoglycoside Antibiotics

Chemistry for the efficient modification of the kanamycin class of 4,6-aminoglycosides at the 4′-position is presented. In all kanamycins but kanamycin B, 4′-<i>O</i>-alkylation is strongly detrimental to antiribosomal and antibacterial activity. Ethylation of kanamycin B at the 4″-position entails little loss of antiribosomal and antibacterial activity, but no increase of ribosomal selectivity. These results are contrasted with those for the 4,5-aminoglycosides, where 4′-<i>O</i>-alkylation of paromomycin causes only a minimal loss of activity but results in a significant increase in selectivity with a concomitant loss of ototoxicity