A synthesis of the chlorosulfolipid mytilipin A via a longest linear sequence of seven steps.

Magnificent seven: The chlorosulfolipid mytilipin A was synthesized in racemic form in seven steps and in enantioenriched form in eight steps. Key transformations include a highly diastereoselective bromoallylation of a sensitive α,β-dichloroaldehyde, a kinetic resolution of a vinyl epoxide, a convergent and highly Z-selective alkene cross-metathesis, and a chemoselective and diastereoselective dichlorination of a complex diene.

Chlorosulfolipids: structure, synthesis, and biological relevance.

Chlorosulfolipids have been isolated from freshwater algae and from toxic mussels. They appear to have a structural role in algal membranes and have been implicated in Diarrhetic Shellfish Poisoning. Further fascinating aspects of these compounds include their stereochemically complex polychlorinated structures and the resulting strong conformational biases, and their poorly understood (yet surely compelling) biosynthesis.

A concise enantioselective synthesis of the chlorosulfolipid malhamensilipin A.

The first enantioselective synthesis of a member of the chlorosulfolipid family of natural products is reported. All of the polar substituents of malhamensilipin A are introduced with high stereoselectivity, and the unique (E)-chlorovinyl sulfate is created by a chemo-, regio-, and stereoselective E2 elimination of HCl in a reaction that likely has a counterpart in the biosynthesis of this fascinating natural product.

Relative stereochemistry determination and synthesis of the major chlorosulfolipid from Ochromonas danica.

The relative stereochemistry of the major chlorosulfolipid of the chrysophyte alga Ochromonas danica, to which we have given the name "danicalipin A", is reported. The first synthesis of this lipid, via several stereospecific electrophilic additions to alkenes, serves to corroborate the stereochemical assignment made by NMR spectroscopy. The synthesis strategy described should be applicable to other chlorosulfolipids and should provide access to sufficient material for studies of the lipid's properties and function in membranes.

Phase-transfer-catalyzed asymmetric acylimidazole alkylation.

2-Acylimidazoles are alkylated under phase-transfer conditions with cinchonidinium catalysts at -40 degrees C with allyl and benzyl electrophiles in high yield with excellent enantioselectivity (79 to >99% ee). The acylimidazole substrates are made in three steps from bromoacetic acid via the N-acylmorpholine adduct. The catalyst is made in high purity allowing for S-product formation (6-20 h) under mild conditions, consistent with an ion-pair mechanism.

Total synthesis of the hydroxyketone kurasoin A using asymmetric phase-transfer alkylation.

The total synthesis of the farnesyltransferase inhibitor kurasoin A has been achieved using a novel asymmetric phase-transfer-catalyzed glycolate alkylation reaction. 2,5-Dimethoxyacetophenone 7 with cinchonidinium catalyst 9(10 mol %) and hydroxide base with pivaloyl benzyl bromide 8 provided S-alkylation product 10 in high yield (80-99%) and excellent enantioselectivity. Baeyer-Villiger oxidation, Weinreb amide formation, and benzyl Grignard addition to the TES-ether 17 gave the protected target.

Asymmetric phase-transfer catalyzed glycolate alkylation, investigation of the scope, and application to the synthesis of (-)-ragaglitazar.

[Reaction: see text]. Asymmetric glycolate alkylation using a protected acetophenone surrogate under solid-liquid phase-transfer conditions is a new approach to the synthesis of 2-hydroxy esters and acids. Diphenylmethyloxy-2,5-dimethoxyacetophenone 1 with a trifluorobenzyl cinchonidinium bromide catalyst 9 (10 mol %) and cesium hydroxide provided S-alkylation products 2 at -35 degrees C in high yield (80-99%) and with excellent enantioselectivities using a wide range of electrophiles (80-90% ee).