Metal-catalyzed enantioselective allylation in asymmetric synthesis

Metal-catalyzed enantioselective allylation, which involves the substitution of allylic metal intermediates with a diverse range of different nucleophiles or S(N)2'-type allylic substitution, leads to the formation of C-H, -C, -O, -N, -S, and other bonds with very high levels of asymmetric induction. The reaction may tolerate a broad range of functional groups and has been applied successfully to the synthesis of many natural products and new chiral compounds.     

Chemistry and biology of the aeruginosin family of serine protease inhibitors

The aeruginosins have been isolated from marine sponges and cyanobacterial waterblooms, sources that are phylogenetically distinct and the bodies of water are geographically well-separated. The aeruginosins comprise a central hydroxy- (or dihydroxy-) octahydroindole carboxamide core unit, onto which are appended unusual amino acids on the carboxy and amino termini as part of the linear peptide array. Potent inhibitory activity of serine proteases in vitro is exhibited by some of the aeruginosins as a result of the presence and proper deployment of three important pharmacophoric subunits: a P1 arginine mimetic, and two hydrophobic residues with interaction sites designated as P2 and P3. In this article, we provide the first comprehensive review on the chemistry and biology of the aeruginosins, with an emphasis on their sources, structural revisions, and total syntheses.     

Orthidines A-E, tubastrine, 3,4-dimethoxyphenethyl-β-guanidine, and 1,14-sperminedihomovanillamide: potential anti-inflammatory alkaloids isolated from the New Zealand ascidian Aplidium orthium that act as inhibitors of neutrophil respiratory burst

In addition to the known dihydroxystyrylguanidine alkaloid tubastrine (1), five new dimers, orthidines A-E (2-6) and the biosynthetically unrelated 1,14-sperminedihomovanillamide (orthidine F, 7) were isolated from the New Zealand ascidian Aplidium orthium. The structures of the new compounds, elucidated by interpretation of spectroscopic data, encompass benzodioxane neolignan-type scaffolds (2-5) and a 1,2,3,4-tetrasubstituted cyclobutane (6), the latter likely having arisen via [_π2_s+_π2_s] dimerization of tubastrine. The subunit head-to-tail orientation of dimer 6 was established unambiguously by interpretation of data from a ²J,³J-HMBC NMR experiment. The structure of 7 was also confirmed by facile synthesis. Compounds 1-4, 6, and 7 inhibited the in vitro production of superoxide by PMA-stimulated human neutrophils in a dose-dependent manner with IC₅₀s of 10-36 μM and this was associated with inhibition of superoxide production by neutrophils in vivo in a murine model of gouty inflammation.     

Titanocene(III) chloride mediated radical-induced synthesis of 3,4-dihydroisocoumarins: synthesis of (±)-hydrangenol, (±)-phyllodulcin, (±)-macrophyllol and (±)-thunberginol G

A radical-promoted synthesis of 3,4-dihydroisocoumarins has been achieved in moderate to good yields using titanocene(III) chloride (Cp₂TiCl) as the radical initiator. The total synthesis of four naturally occurring dihydrocoumarins hydrangenol, phyllodulcin, macrophyllol and thunberginol G has been accomplished using the radical technology. Cp₂TiCl was prepared in situ from commercially available titanocene dichloride (Cp₂TiCl₂) and Zn-dust in THF under argon.     

Chiral building blocks from d-xylose and their application in synthesis of avocadotriol monoacetate

Facile routes to several enantiomerically pure flexible chiral building blocks carrying a hidden syn or anti 1,3-diol motif were developed with the inexpensive and readily available carbohydrate d-xylose as the starting material. Application of the newly developed chiral building blocks in total synthesis is exemplified through a synthesis of (2S,4S)- and (2S,4R)-avocadotriol. Both triols were selectively acetylated on the primary hydroxyl group in high yields with Novozyme 435/vinyl acetate. On the basis of comparison of the ¹H NMR, optical rotation, and melting point data, the natural avocadotriol 1-monoacetate was assigned to be of (2R,4R) configuration.