A simple and efficient highly enantioselective synthesis of alpha-ionone and alpha-damascone.

An efficient highly enantioselective (ee > or =99%) synthesis of alpha-ionone and alpha-damascone is described. Both enantiomers of title compounds were synthesized through two straightforward pathways diverging from enantiopure (R)- or (S)-alpha-cyclogeraniol. These versatile building blocks were obtained by regioselective ZrCl(4)-promoted biomimetic cyclization of (6S)- or (6R)-(Z)-6,7-epoxygeraniol, respectively, followed by deoxygenation of the so formed secondary alcohol. The chiral information was encoded by a highly regioselecive Sharpless asymmetric dihydroxylation of inexpensive geranyl acetate.

A --> J prostaglandin swap: a new tactic for cyclopentenone prostaglandin synthesis.

A practical methodology for the synthesis of J-type prostaglandins has been developed starting from the well-consolidated approaches established for the synthesis of A-type prostaglandins. An efficient 1,3-allylic transposition of the C-9 hydroxyl group of intermediate 4 furnished the advanced precursor 5 for J(2) synthesis. Our optimized A-J swap protocol employed selenium chemistry, involving the [2,3] sigmatropic rearrangement of secondary allylic selenoxide 11a.

First enantioselective total synthesis of (8S,12R,15S)-prostaglandin J(2).

Enantioselective synthesis of natural PGJ(2) has been accomplished for the first time starting from the commercially available enantiopure aldehyde 7 in 10% overall yield. The key reaction was a novel prostaglandin class interconversion, i.e., an allylic 1,3-transposition across alcohol 9 derived from compound 14 in 73% overall yield. In principle, the unnatural enantiomer of PGJ(2) could be obtained starting from the commercially available enantiopure monobenzoate 7a following our strategy.

First total synthesis of JS isoprostane.

A stereoselective Julia-Lythgoe olefination followed by an efficient 1,3-allylic transposition of the C-9 hydroxyl group of compound 13 has allowed the first total synthesis of J(2) isoprostane (1), a recently discovered member of the growing isoprostane family. This elusive compound opens up numerous new avenues for the molecular biology of cyclopentenone prostaglandins which are endowed of intriguing biological effects such as antitumor, antiinflammatory, and antiviral activities. In principle, our approach is flexible enough to allow an easy synthesis of other isoprostanes of the J family following the same methodology.

Toggling enantioselective catalysis--a promising paradigm in the development of more efficient and versatile enantioselective synthetic methodologies.

The increasingly needed synthesis of both enantiomers of a chiral compound usually requires the use of both enantiomers of a chiral catalyst. Several of the usually employed chiral ligands are naturally available in only one enantiomeric form, the antipode often being of labor-intensive preparation. Enantiodivergent asymmetric catalysis has accrued in importance in this regard, in that it allows expeditious access to both enantiomers of a product without any direct modification on the chemical structure of the chiral promoter. Various promising examples will be discussed throughout the review. If available or envisageable, a mechanistic rationale for the observed enantioinversion will be outlined.