Acetogenic Isoquinoline Alkaloids, LXXXII. Biomimetic Total Synthesis of Michellamines A–C

Abstract

The biomimetic first total synthesis of michellamines A, B, and C (la-c), naturally occurring quateraryl alkaloids with high anti-HIV activity, is described. Key precursors are the molecular "halves" of michellamines, the antimalarial naphthylisoquinoline alkaloids korupensamine A (2a) and B (2b), which are likewise natural products. These "monomeric" naphthylisoquinoline alkaloids were prepared by Stille-type intermolecular aryl coupling of the 0-isopropyl-protected and trialkylstannyl-activated naphthalene building block 4 b Lo]Me OH Me OH l a OH Me Ib OH Me Me OH OH M Me ' O w M e \ N. " IC OH Medispose of four stereogenic centers and three biaryl axes, of which the two outer ones are stereogenic, whereas the inner one, which links the constitutionally identical molecular "halves", is conformatively unstable. The constitution and

The Lactone Concept: An Efficient Pathway to Axially Chiral Natural Products and Useful Reagents

“…Therefore our first total synthesis of these antimalarial 141 naphthylisoquinolines had to rely on an LQWHUPROHFXODU coupling step, which was best performed by a Stille coupling of with . 116,117 Because of the presence of only three RUWKR-substituents next to the axis and hence the reduced steric hindrance, this did work, but the coupling yields were low and the atropo-diastereoselectivities very moderate. Subsequent other syntheses either did not give better results 143-145 or did not lead to the authentic natural products, 30c,144,145 only to korupensamine GHULYDWLYHV.…”

“…We were lucky to be the first to develop chemical, 149,117 but also enzymic, 150,151 methods to dimerize korupensamines to give michellamines. 152 Of these, in particular michellamine B constitutes a novel anti-AIDS lead structure.…”

Atroposelective Total Synthesis of the Fourfold ortho‐Substituted Naphthyltetrahydroisoquinoline Biaryl O,N‐Dimethylhamatine

“…Cyclization under Bischler–Napieralski conditions gave the derived cyclic imine, to which was added MeMgCl in a mix of THF/diethyl ether at low temperature to afford the desired trans ‐product 20 in quantitative yield. Several attempts at iodination of the aryl ring in 20 using known methodologies, such as AgSO 4 /iodine, as well as hypervalent iodine salts gave both large amounts of oxidized products and poor regioselectivity . A newly designed method that generated the desired material regioselectively involved use of NIS/TFA, after which N ‐methylation went smoothly under mild reductive amination conditions with paraformaldehyde and catalytic amounts of formic acid to form 21 .…”

Synthesis of Biaryl Compounds through Three‐Component Assembly: Ambidentate Effect of the tert‐Butyldimethylsilyl Group for Regioselective Diels–Alder and Hiyama Coupling Reactions

“…Thus, anti ‐ 4 j was selectively converted into 8‐TBDMS‐4‐stannyl‐1‐naphthol 5 j in the presence of [Cp*RuCl(cod)] (0.15 equiv; Cp*=C 5 Me 5 , cod=1,5‐cyclooctadiene). The tributylstannyl group, which can be replaced with various aryl groups by Stille coupling reactions, remained intact 11. Although the Diels–Alder reaction of 2‐phenylfuran ( 2 d ) exhibited little selectivity (Table 2, entry 5), the series of a regioselective Diels–Alder reaction with 2‐stannylfuran ( 2 f ), a ring‐opening reaction, and a Stille coupling is a highly reliable method for the regioselective synthesis of 8‐TBDMS‐4‐aryl‐1‐naphthols 5 d′ [Eq.…”