Total Synthesis of Aflastatin A.

The total syntheses of aflastatin A and its C3-C48 degradation fragment (, R = H) have been accomplished. The syntheses feature several complex diastereoselective fragment couplings, including a Felkin-selective trityl-catalyzed Mukaiyama aldol reaction, a chelate-controlled aldol reaction involving soft enolization with magnesium, and an anti-Felkin-selective boron-mediated oxygenated aldol reaction. Careful comparison of the spectroscopic data for the synthetic C3-C48 degradation fragment to that reported by the isolation group revealed a structural misassignment in the lactol region of the naturally derived degradation product.

Molecular editing and biological evaluation of amphidinolide X and Y.

Scarce and precious: A collection of compounds with deep-seated structural "point mutations" within the framework of the marine natural products amphidinolide X and Y was prepared by "diverted total synthesis". The resulting products provided first insights into the cytotoxicity profile of these extremely scarce macrolides.Deliberate deviations from the previously described total syntheses of amphidinolide X (1) and Y (2) allowed a collection of seven designed analogues of these extremely scarce marine natural products to be obtained.

A cheap metal for a "noble" task: preparative and mechanistic aspects of cycloisomerization and cycloaddition reactions catalyzed by low-valent iron complexes.

Reaction of ferrocene with lithium in the presence of either ethylene or COD allows the Fe(0)-ate complexes 1 and 4 to be prepared on a large scale, which turned out to be excellent catalysts for a variety of Alder-ene, [4+2], [5+2], and [2+2+2] cycloadditon and cycloisomerization reactions of polyunsaturated substrates. The structures of ferrates 1 and 4 in the solid-state reveal the capacity of the reduced iron center to share electron density with the ligand sphere. This feature, coupled with the kinetic lability of the bound olefins, is thought to be responsible for the ease with which different enyne or diyne substrates undergo oxidative cyclization as the triggering event of the observed skeletal reorganizations.

Total syntheses of amphidinolide X and Y.

Concise total syntheses of the cytotoxic marine natural products amphidinolide X (1) and amphidinolide Y (2) as well as of the nonnatural analogue 19-epi-amphidinolide X (47) are described. A pivotal step of the highly convergent routes to these structurally rather unusual secondary metabolites consists of a syn-selective formation of allenol 17 by an iron-catalyzed ring opening reaction of the enantioenriched propargyl epoxide 16 (derived from a Sharpless epoxidation) with a Grignard reagent. Allenol 17 was then cyclized with the aid of Ag(I) to give dihydrofuran 19 containing the (R)-configured tetrasubstituted sp3 chiral center at C.

Total synthesis of amphidinolide X.

A concise total synthesis of the cytotoxic marine natural product amphidinolide X (1) is described. A key step of the highly convergent route to this structurally rather unusual macrodiolide derivative consists of a newly developed, highly syn selective formation of allenol 6 by an iron-catalyzed ring opening reaction of the enantioenriched propargyl epoxide 5 (derived from a Sharpless epoxidation) with a Grignard reagent. Allenol 6 was then cyclized with the aid of Ag(I) to give dihydrofuran 7 containing the (R)-configured quarternary sp3 chiral center at C19 of the target.

Counterion-directed regioselective acetylation of octyl beta-D-glucopyranoside.

[reaction: see text] The DMAP-catalyzed acetylation of octyl beta-D-glucopyranoside with a series of acetylating agents has been investigated. The nature of the counterion of the catalytic DMAP-acetyl complex dramatically influences the outcome of the reaction, indicating that the deprotonation of the transition state is controlling the reaction. Noncovalent interactions of the acetate ion with the substrate seem to direct the acetylation toward secondary hydroxyl groups.