Substrate Promiscuity of a Paralytic Shellfish Toxin Amidinotransferase.

Secondary metabolites are assembled by enzymes that often perform reactions with high selectivity and specificity. Many of these enzymes also tolerate variations in substrate structure, exhibiting promiscuity that enables various applications of a given biocatalyst. However, initial enzyme characterization studies frequently do not explore beyond the native substrates.

Functionalized Cyclopentanes via Sc(III)-Catalyzed Intramolecular Enolate Alkylation.

We report herein the intramolecular α--alkylation of unsaturated β-ketoesters which gives rise to highly functionalized cyclopentanes. This strategy is characterized by its operational simplicity, mild reaction conditions and the use of scandium(III) triflate as a Lewis acid catalyst. Of interest, cyclopentanes bearing heterocycles, sites for post reaction functionalization and spirocyclic architectures are accessible with this strategy.

C-H Hydroxylation in Paralytic Shellfish Toxin Biosynthesis.

The remarkable degree of synthetic selectivity found in Nature is exemplified by the biosynthesis of paralytic shellfish toxins such as saxitoxin. The polycyclic core shared by saxitoxin and its relatives is assembled and subsequently elaborated through the installation of hydroxyl groups with exquisite precision that is not possible to replicate with traditional synthetic methods. Here, we report the identification of the enzymes that carry out a subset of C-H functionalizations involved in paralytic shellfish toxin biosynthesis.

Total synthesis of [ C] -, [ C] -, and [ C] -isotopomers of xanthohumol, the principal prenylflavonoid from hops.

Xanthohumol [(E)-6'-methoxy-3'-(3-methylbuten-2-yl)-2',4',4″-trihydroxychalcone], he principal prenylated flavonoid from hops, has a complex bioactivity profile, and C-labeled isotopomers of this compound are of potential use as molecular probes and as analytical standards to study metabolism and mode of action. 1,3-[ C] -Xanthohumol was prepared by an adaptation of the total synthesis of Khupse and Erhardt in 7 steps and 5.7% overall yield from phloroglucinol by a route incorporating a cascade Claisen-Cope rearrangement to install the 3'-prenyl moiety from a 5'-prenyl aryl ether and an aldol condensation between 1-[ C]-2',4'-bis(benzyloxymethyloxy)-6'-methoxy-3'-(3-methylbuten-2-yl)acetophenone and 1'-[ C]-4-(methoxymethyloxy)benzaldehyde.