Yikang Wu

A Broadly Applicable Mild Method for the Synthesis of gem-Diperoxides from Corresponding Ketones or 1,3-Dioxolanes

Ketones or ketals were readily converted into the corresponding gem-dihydroperoxides in high yields by treatment with ethereal H(2)O(2) at ambient temperature in the presence of 2-5 mol % of phosphomolybdic acid.

Facile ring-opening of oxiranes by H(2)O(2) catalyzed by phosphomolybdic acid.

At ambient temperature, in the presence of catalytic amounts of phosphomolybdic acid (PMA), ethereal hydrogen peroxide reacted readily with a range of epoxides, giving corresponding beta-hydroxyhydroperoxides in high yields.

Preferential hydrolysis of benzylic/allylic dithianes and dithiolanes using o-iodoxybenzoic acid (IBX) in DMSO containing traces of water

Dithianes and dithiolanes at benzylic or allylic carbons can easily be hydrolyzed by IBX in DMSO, whereas non-activated dithianes/dithiolanes are much more stable under these conditions.

A hydrogen peroxide based access to qinghaosu (artemisinin).

Attachment of H(2)O(2) onto the highly hindered quaternary C-12a in an advanced qinghaosu (artemisinin) precursor has been achieved through a facile perhydrolysis of a spiro epoxy ring with the aid of a previously unknown molybdenum species without involving any special equipment or complicated operations. The resultant β-hydroxyhydroperoxide can be further elaborated into qinghaosu, illustrating an entry fundamentally different from the existing ones to this outstanding natural product of great importance in malaria chemotherapy.

Potent antimalarial 1,2,4-trioxanes through perhydrolysis of epoxides.

Perhydrolysis of a sterically congested multifunctional epoxide was achieved in ethereal H2O2 with the aid of a recently developed Mo catalyst. The resulting hydroperoxide cyclized to give a 1,2,4-trioxane, which could be readily elaborated into qinghaosu and a range of novel analogues. Some of the compounds with two such trioxane moieties showed in vitro antimalarial activity comparable to or even better than that of artesunate or chloroquine.

An enantioselective convergent route to pamamycin 621A.

An effective approach to the total synthesis of natural antibiotic pamamycin 621A is described, in which the stereogenic centers at the C-13 and C-15 were taken from a chiral building block derived from the inexpensive D-glucolactone while all others (except the C-10) were installed via chiral auxiliary-induced asymmetric Evans/Crimmins aldol reactions. In the synthesis of the smaller/lower fragment, an antiselective Evans aldol condensation was found to occur only if a stoichiometric (rather than catalytic as reported in the literature) amount of magnesium chloride was present. A previously unknown effect of the steric bulkiness of the pyridine base employed on the stereochemical outcome of the formation of the THF ring in the presence of a chiral auxiliary was also observed. The THF rings in the larger/upper fragment were similarly synthesized with a high level of stereoselectivity from a linear precursor carrying a chiral auxiliary via intramolecular O-alkylations, most notably even under acidic conditions. The basic dimethylamino functionality at the C-15 was installed at the final stage of the whole synthesis, with those otherwise unavoidable side reactions in the conversion of the azido group effectively circumvented through using a very mild yet largely forgotten tributyltin reduction protocol.

Simple analogues of qinghaosu (artemisinin).

A series of 1,2,4-trioxanes were synthesized in which the key peroxy bonds were installed through a molybdenum-catalyzed perhydrolysis of the epoxy rings. A core structure was identified that may serve as a promising lead structure for further investigations because of its high antimalarial activity (comparable to that of artesunate and chloroquine), apparent potential for scale-up and derivatization, and facile monitoring/tracing by using UV light.

A practical approach to the synthesis of insect antifeedant tonghaosu analogs

Tonghaosu and its analogs are a clas of structurally interesting spiroketal enol-ether compounds. A practical route to furandiol, a key intermediate for their syntheses, was developed. Using Friedel-Crafts benzoylaton of 3-(2-furyl) propyl acetate, a diarylketone was obtained in high yield, which was further transformed into corresponding furandiol by reduction with NaBH^4 in basic medium with simultaneous ester hydrolysis. The furandiol was then cyclized into the desired spiroketal enol-ether compound in the presence of CuSO^4.5H^2O.

An Expeditious Access to Enantiomerically Pure cis‐Dialkyl‐Substituted γ‐ and δ‐Lactones

A facile general route to enantiomerically pure 3,4-cis-dialkyl-substituted γ-lactones and 4,5-cis-dialkyl-substituted δ-lactones by TiCl4-mediated Evans asymmetric aldolization as the key step is exemplified by synthesis of cis-(3R,4R)-3-methyldecan-4-olide and (4R,5R)-aerangis lactone.

Synthesis and Absolute Configuration of Demethyl (C‐11) Cezomycin

The synthesis of (-)-demethyl (C-11) cezomycin was achieved through an efficient route that features the use of a Kulinkovich reaction to couple two multifunctionality-containing fragments and a cascade of ring opening of cyclopropanol/1,5-hydrogen shift/desilylation-oxidation. The hidden yet undeniable problem of irreproducible specific rotation for this family of compounds was solved by sufficient acidification. The absolute configuration for the natural product was thus established as the mirror image of the synthetic sample.