Jas S. Ward

Modular Total Syntheses of the Marine-Derived Resorcylic Acid Lactones Cochliomycins A and B Using a Late-Stage Nozaki–Hiyama–Kishi Macrocyclization Reaction

The natural products cochliomycin A (1) and cochliomycin B (2), two resorcylic acid lactones obtained from marine sources, have been prepared in a concise and stereocontrolled manner from the readily accessible building blocks 4-6. Olefin cross-metathesis, trans-esterification and Nozaki-Hiyama-Kishi (NHK) macrocyclization reactions were employed in the key steps. Hydrolysis of the immediate precursor to cochliomycin B affords the resorcylic acid lactone zeaenol (24).

Total syntheses of the resorcylic acid lactone neocosmosin A and its enantiomer.

A total synthesis of the structure, 1, assigned to the recently reported resorcylic acid lactone (RAL) neocosmosin A has been established. Olefin-cross metathesis, ring-closing metathesis, palladium-catalyzed Meinwald rearrangement, and Mitsunobu esterification reactions were used as key steps. A late-stage and simple modification to the reaction sequence also provided compound ent-1 that, in fact, represents the true structure of the natural product.

Halogen Substitution Effects on N2O Schiff Base Ligands in Unprecedented Abrupt FeII Spin Crossover Complexes

A family of halogen-substituted Schiff base iron(II) complexes, [FeII (qsal-X)2 ], (qsal-X=5-X-N-(8-quinolyl)salicylaldimines)) in which X=F (1), Cl (2), Br (3) or I (4) has been investigated in detail. Compound 1 shows a temperature invariant high spin state, whereas the others all show abrupt spin transitions, at or above room temperature, namely, 295 K (X=I) up to 342 K (X=Br), these being some of the highest T1/2 values obtained, to date, for FeII N/O species. We have recently reported subtle symmetry breaking in [FeII (qsal-Cl)2 ] 2 with two spin transition steps occurring at 308 and 316 K. A photomagnetic study reveals almost full HS conversion of [FeII (qsal-I)2 ] 4 at low temperature (T(LIESST)=54 °K). The halogen substitution effects on the magnetic properties, as well as the crystal packing of the [FeII (qsal-X)2 ] compounds and theoretical calculations, are discussed in depth, giving important knowledge for the design of new spin crossover materials. In comparison to the well known iron(III) analogues, [FeIII (qsal-X)2 ]+ , the two extra π-π and P4AE interactions found in [FeII (qsal-X)2 ] compounds, are believed to be accountable for the spin transitions occurring at ambient temperatures.

Chemoenzymatic total synthesis and reassignment of the absolute configuration of ribisin C.

The enantiomerically pure and enzymatically derived cis-1,2-dihydrocatechol 5 has been converted, by two related pathways, into compounds 3 and ent-3. As a result, it has been determined that the true structure of the natural product ribisin C is represented by ent-3.

A Total Synthesis of the Antifungal Deoxyaminocyclitol Nabscessin B from l-(+)-Tartaric Acid

Aminocyclitol 2, a recently isolated and notable antifungal agent, was prepared from homochiral γ-hydroxycyclohexenone 4, which is itself available in six steps from l-(+)-tartaric acid (3). The well-defined rigidifying effect arising from the 1,2-diacetal protecting group associated with compound 4 and its derivatives allows for high levels of regio- and stereo-chemical control in the manipulation of the cyclitol framework.

Total Synthesis of the Marine Alkaloid Discoipyrrole C via the MoOPH-Mediated Oxidation of a 2,3,5-Trisubstituted Pyrrole

A total synthesis of the marine alkaloid discoipyrrole C (3) is described. In the pivotal step, the 2,3,5-trisubstituted pyrrole 19 was treated with MoOPH in the presence of MeOH, and the resulting methoxylated 1,2-dihydro-3H-pyrrol-3-one 20 subjected to reaction with potassium carbonate in MeOH then trifluoroacetic acid and H2O. This gave a mixture of target 3 and its dehydration product, and the structure of the former compound was confirmed by single-crystal X-ray analysis.

A Chemoenzymatic Route to the (+)-Form of the Amaryllidaceae Alkaloid Narseronine*

We thank the Australian Research Council and the Institute of Advanced Studies for generous financial support.

Synthetic Studies on the Natural Product Myrsinoic Acid F Reveal Biologically Active Analogues

The synthesis of the structure, 1, assigned to the anti-inflammatory natural product myrsinoic acid F is reported together with a means for preparing its Z-isomer 21. While neither of these compounds corresponds to the natural product, both of them are anti-inflammatory agents (as determined using a mouse ear edema assay) with congener 1 being notably more potent than the widely prescribed NSAID indometacin.

Syntheses of Structurally and Stereochemically Varied Forms of C7N Aminocyclitol Derivatives from Enzymatically Derived and Homochiral cis-1,2-Dihydrocatechols

The structurally and stereoisomerically varied C7N aminocyclitol derivatives 2-4 have been prepared, using a versatile and flexible range of protocols, from the cis-1,2-dihydrocatechols 5 and 6, homochiral metabolites derived from the whole-cell biotransformation of the corresponding halobenzene. Reaction sequences that enable syntheses of the enantiomeric forms of these derivatives have also been established.

Palladium-Catalyzed Ullmann Cross-Coupling of β-Iodoenones and β-Iodoacrylates with o-Halonitroarenes or o-Iodobenzonitriles and Reductive Cyclization of the Resulting Products To Give Diverse Heterocyclic Systems

The palladium-catalyzed Ullmann cross-coupling of β-iodoenones and β-iodoacrylates such as 5 (X = I) with o-halonitroarenes and o-iodobenzonitriles including 2 affords products such as compound 7. These can be engaged in a range of reductive cyclization reactions leading to heterocyclic frameworks such as 3,4-benzomorphan derivative 43.