Michellamines A and

The products from Step 1 were dissolved in 2 ml methyl alcohol containing a trace amount of 10% palladium on carbon and hydrogenated 3 days at ambient pressure. After removal of the solvent, the residue was dissolved in 5 ml methanolic HCl, refluxed 10 hours, and the products isolated as a Michellamine A and B mixture in 85% yield, mp = 175-177 °C. H-NMR data supplied. 

Bringmann, G., Gulden, K. P., Busemann, S., Calculation of circular dichroism spectra of michellamines A and C, based on a complete conformational analysis. Tetrahedron 2003, 59, 1245-1253. 

Most recently, the anti-HIV alkaloids michellamines A and B have snccessfully been synthesized by a double Suzuki-type cross-coupling reaction between a binaphthalene ditriflate and an isoquinoUneboronic acid (Scheme... 

Biaryls containing three or four ortho substituents are discrete from the others in that they can exist as persistent atropisomers that are chiral. There are even a number of natural products containing such chiral biaryl moieties including michellamines A and B and vancomycin. These compounds provide some of the ultimately chal-... 

The isomeric michellamines A, B, and C are active against human immunodeficiency virus (HTV)-1 and HIV-2 strains. Michellamines A and B, both having identical tetrahydroisoquinoUne structures and different configurations at the biaiy 1 axes, are synthesized by a simultaneous double-coupling of the di-triflate (Eq. A highly hindered... 

These related reactions have been utilized for total syntheses of natural products such as makaluvamine D (54), makaluvamine I (55), makaluvamine M (56), makaluvamine F (57), and michellamine A (58). Furthermore, synthetic studies on ellagitannin (59),benzo[c]phenanthridines (60), and rebeccamycin (61) have also been carried out. 

Recently, the anti-HIV alkaloids michellamines A (4) and B (5) have attracted much attention. The tetraaryl skeleton of the michellamines is constructed by first forming the inner (nonstereogenic) biaryl axis and then adding the two other (stereogenic) axes by means of a double Suzulci-type cross-coupling reaction between binaphthalene ditriflate (2) and iso-quinolineboronic acid (3) (Eq. (13)) [31]. 

Another total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B has been developed by Hoye et al. [32], who emphasized that Suzuki coupling of the boronic acid derived from the naphthalene moiety with a THIQ-iodide proved to be the most generally effective method for forming the hindered biaryl bond. A racemic isochromane analogue of michellamines has been synthesized by a similar procedure [33]. 

The dimeric stereoisomer alkaloids michellamines A, B and C (38) were obtained From the liane Ancistrocladus korupensis (Ancistrocladaceae). On the basis of their structural similarity to other PKC inhibitors, they have been studied for this activity. Michellamines inhibited rat brain PKC, with IC50 values in the 15-35 pM range. Michellamine B was a non-competitive PKC inhibitor with respect to ATP, whereas mixed-type inhibition was observed when the peptide concentration varied. The results indicate that the dimeric alkaloids bind to the PKC kinase domain and not to its regulatory domain. All three michellamines blocked both the ATP and the... 

NEt3- The resulting binaphylidendione 211 was then carefully reduced with sodium borohydride and deprotection was effected in a single step with methanolic HCl to provide michellamine A (6). 

Five naphthylisoquinoline alkaloids (dimers michellamine A, B, and C, and momomers korupensamine A and B) were separated on a Cjg column (positive ion electrospray MS, collision energy 25 eV collision pressure 2.5mTorr) using a complex 19-min 85/15 -> 60/40 water (0.1% TFA)/acetonitrile gradient [1171]. Test solution concentrations were 20ng/mL. 

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