Peter T. Lansbury

SYNTHESIS OF (+)-ARTEMISININ AND (+)-DEOXOARTEMISININ FROM ARTEANNUIN B AND ARTEANNUIC ACID

Abstract (+)-Artemisinin and (+)-Deoxoartemisinin were prepared for the first time from arteannuin B. The synthetic route is short and efficient, making use of the prior art for the final photo-oxygenation/cyclization reaction. A convergent route to each of the above-named products from arteannuic acid is also described. A novel oxidative lactonization reaction was developed for this sequence.

An efficient partial synthesis of (+)-artemisinin and (+)-deoxoartemisinin

Abstract Arteannuic acid and arteannuin B are separately convertible into intermediate 8 , which is transformed by four or five high-yielding steps into the title anti-malarial sesquiterpene peroxides.

Total synthesis of (±)-arteannuin B

Abstract The title compound has been synthesized beginning with 4-methyl-2-cyclohexen-1-one, using intramolecular hydroxyl-directed reactions to achieve regio- and stereoselectivity at important stages.

Total synthesis of pseudoguaianes—I: Preparation of bicyclo[5.3.0]decane synthons for damsinic acid and helenanolides

Abstract A reaction sequence has been developed for preparing hydroazulenones suitable for total synthesis of pseudoguaiane sesquiterpenes (→1 →2 →4). The relative configuration of bicyclic ketone 2 at three chiral centers was established by its conversion to (±)-damsinic acid (3). Subsequently, the C-10 chiral center of 2 was inverted by employing temporary vinyl activation (2 →27 →4). Ketone 4 thus produced is a potential synthon for helenanolides, having the required configuration at carbons 1, 5 and 10 found in that class of sesquiterpene lactones.

Superior methodology for γ-lactone annulation: intramolecular : Alkoxyhydride reduction of conjugated nitriles

Abstract Metal hydride reduction of acetate groups adjacent on rings to exocyclic α,β-unsaturated nitriles generates alkoxyhydrides which perform stereospecific intramolecular hydride transfers to the β-position of the conjugated system; hydrolysis of the γ-hydroxynitriles so formed gives, after lactonization, trans -fused γ-butyrolactones whose relative stereochemistry is derived from the configuration of the original acetate.

Total synthesis of (±)-12-noralliacolide, (±)-alliacol A and (±)-alliacolide

Abstract The title compounds were prepared via a “one-pot” γ-lactone annulation sequence in which dilithium acetate functions as a bis -nucleophile, first at carbonyl and then at hindered allylic sulfonate centers (SN′ orientation).

Total synthesis of pseudoguaianolides V Stereocontrolled approaches to the fastigilins: (±)-2, 3-Dihydrofastigilin C

Abstract A synthetic route to highly-oxygenated pseudoguaianolide intermediates has been developed. The functional groups on the seven-membered rings were introduced stereoselectively at all seven chiral centers. In addition, regioaelective esterification at C-6 hydroxyl groups, in the presence of a C-9 hydroxyl site, was achieved.

Conjugative γ-lactone annulation: one-pot hydroboration : Oxidation of homoallylic alcohol trimethylsilyl ethers

Abstract Products from stereospecific vinylcuprate addition to hydroazulenic γ-trimethylsiloxy-α,β-unsaturated cycloheptenones are converted directly to trans -fused γ-lactones by 1) BH3-THF, 2) B-H hydrolysis, and 3) PCC oxidation.

Symmetry-enhanced remote dicarbanion annulations for latent cycloalkenones: Applications to alkaloids and terpenes

Abstract Functionalized 1,n-dicarbanions (n=4, 5, 6) react with α, α′-methallyl dihalides to produce n+3 substituted α-methylenecycloalkanes that are synthetic equivalents of two differentiable cycloalkenones.

An enantioselective approach to chiral pseudoguaianolide intermediates

The viability of an enantioselective route to pseudoguaianolides has been established with the construction of hydroazulenone 3, whose absolute configuration parallels that of radiatin.