Search

A convergent synthesis of the structure proposed for the naturally occurring lactone stagonolide G is described. All three stereocenters were created with the aid of asymmetric Brown allylations. The lactone ring was built by means of a ring-closing metathesis (RCM). The synthetic and the natural compound differed in their spectral properties. A new structure is now proposed for stagonolide G and demonstrated by means of a chemical transformation.

[reaction: see text] A stereocontrolled, convergent synthesis of the alkaloid australine, a glycosidase inhibitor of the pyrrolizidine class, is described. The chiral starting materials were ketone 3, derived from L-erythrulose, and alpha-alkoxy aldehyde 4, prepared from L-malic acid. A key step of the synthesis was the highly stereoselective aldol reaction between 4 and a Z boron enolate derived from 3. Another key step was the one-pot construction of the bicyclic pyrrolizidine system by means of a three-step sequence of SN2 displacements induced by benzylamine on a trimesylate precursor.

[reaction: see text] A total synthesis of the naturally occurring, cytotoxic macrolide FD-891 is described. Three fragments were first stereoselectively constructed using mainly asymmetric aldol and allylation reactions. The complete framework was then assembled using two Julia-Kocienski olefinations to connect the three fragments and a Yamaguchi reaction to close the macrolactone ring.

The first total synthesis of the naturally occurring nonenolide, microcarpalide, is described. The key step in the synthesis was the ring-closing metathesis of a dienic ester prepared in turn by coupling an acid and an alcohol stereoselectively synthesized from (S,S)-tartaric acid and (R)-glycidol, respectively. [structure: see text]

Stereoselective syntheses of the delta-lactone of (2Z,5S,7R,9S,11S)-tetrahydroxyhexacos-2-enoic acid, the structure reported for passifloricin A, and of its (5R)-epimer are described. The creation of all stereogenic centers relied upon Brown's asymmetric allylation methodology. The lactone ring was created via ring-closing metathesis. The NMR data of both synthetic products, however, were different from those of the natural product. The published structure of passifloricin A is thus erroneous and will require further synthetic work to be unambiguously assigned. [structure: see text]

Boron aldol additions of variously O-protected alpha,alpha'-dioxygenated ketones using dicyclohexylboron chloride and a tertiary amine have been investigated. The stereoselectivity of the process was dependent on the protecting group on the alpha-oxygen atoms. Notably, ketones with bulky silyloxy groups gave syn aldols, most likely via Z enolates. This rules out the participation of chelates during the enolization process, at least in the presence of such sterically crowded protecting groups. An alternative explanation is offered.