Roland Gotz

Convergent total synthesis of the michellamines

A convergent total synthesis of the anti-HIV michellamines (1) is described. The tetraaryl skeleton of the michellamines was constructed by formation first of the inner (nonstereogenic) biaryl axis and subsequently of the two other (stereogenic) axes in a highly convergent manner. The key transformation features a double Suzuki-type cross-coupling reaction between binaphthalene ditriflate 26 and isoquinolineboronic acid 35. Ditriflate 26 is synthesized in six steps starting from diene 6 and 2,6-dibromobenzoquinone (9) in 21% overall yield. For large scale production of 26, a substantially shortened version of an existing procedure for the preparation of bisnaphthoquinone 13 was also developed, which allows for the preparation of 13 from benzoquinone and diene 6 in five steps and 67% overall yield. Binaphthoquinone 13 was subsequently converted into ditriflate 26 in three steps and 67% overall yield. By the described synthetic strategy, michellamines A (1a) and B (1b) are produced (1a:1b = 1:2.5) in 24.6% ...

‘Biomimetic’ oxidative dimerization of korupensamine A: Completion of the first total synthesis of michellamines A, B, and C

Abstract A first synthetic access to michellamine A (1), a C2-symmetric antiviral naturally occurring quateraryl, is described, by oxidative ‘dimeriza

Synthesis of pindikamine A, a michellamine-related dimer of a non-natural, ‘skew’ naphthylisoquinoline

Abstract The synthesis of an unnatural dimeric naphthylisoquinoline, pindikamine A ( 3 ), as a ‘skew’ analog of antiviral michellamines, is described. Because of the unusual coupling positions, this C 2 -symmetric quateraryl is the first michellamine analog without axial chirality. Key steps of the total synthesis are the preparation of the molecular precursor 9 by intermolecular biaryl coupling, followed by a highly efficient oxidative ‘dimerization’ to give 8 , which is transformed to 3 . Pindikamine A ( 3 ) and its monomeric ‘half’ 10 show good antimalarial activity against Plasmodium falciparum in vitro .

Two Atropisomeric N-Methyldioncophyllines A and N-Methylphylline, their Naphthalene-Free Heterocyclic Moiety, from Ancistrocladus barteri

The West African plant Ancistrocladus barteri (Ancistrocladaceae) was investigated chemically for the first time. Besides the known naphthylisoquinoline alkaloids N-methyldioncophylline A and 7-epi-N-methyldioncophylline A (i.e. its atropo-diastereomer), a new naphthalene-free alkaloid, belonging to the ‘Dioncophyllaceae type’, was isolated. Its structure was elucidated by spectroscopic and degradative methods and confirmed by total synthesis. The new compound, named N-methylphylline, is exactly the isoquinoline “half” of both, N-methyldioncophylline A and its atropisomer. Furthermore, the related tetrahydroisoquinoline O,N-dimethylphylline, an intermediate in the chemical synthesis of N-methylphylline, was detected as a new natural product in crude extracts of A. barteri.