ABSTRACT
[reaction: see text] The synthesis of two model p-quinone methide ring systems of the antibiotic and antiosteoporotic compound kendomycin is reported. Two approaches were examined in detail, and the two-step (i) demethylation and (ii) DMDO oxidation were found to be reliable and generally applicable. Additionally, it was found that oxidation of a benzofuran by NaIO(4) on silica produced a long-lived semiquinone radical.
Subject(s)
Quinones/chemistry , Quinones/chemical synthesis , Rifabutin/analogs & derivatives , Catalysis , Indicators and Reagents , Molecular Structure , Oxidation-Reduction , Rifabutin/chemical synthesis , Rifabutin/chemistry , StereoisomerismABSTRACT
The convergent synthesis of a benzofuran analog of the carbacyclic ansa compound kendomycin has been achieved by assembling three major fragments by means of epoxide opening and directed ortho lithiation. The crucial tetrahydropyran ring was formed by a highly stereoselective cationic cyclization. Analysis of all synthesized tetrahydropyran-arene compounds reveals a hindered sp(2)-sp(3) rotation, which results in rotational isomers or atropisomers affecting macrocyclization reactions. The latter could only be achieved by means of Horner-Wadsworth-Emmons olefination.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Rifabutin/chemical synthesis , Anti-Bacterial Agents/chemistry , Chemistry, Organic/methods , Models, Molecular , Molecular Structure , Rifabutin/analogs & derivatives , Rifabutin/chemistry , StereoisomerismABSTRACT
[reaction: see text] A convergent and concise route to an advanced precursor 2b of kendomycin (1) has been developed by applying a S(N)1 ring cyclization as a key step. The resulting C-aryl glycoside was initially isolated as a rotameric mixture, but after MOM protection of the o-hydroxyl of the phenol, the conformation was frozen to the desired kendomycin-like atropisomer.
