CD-sensitive Zn-porphyrin tweezer host-guest complexes, part 2: cis- and trans-3-hydroxy-4-aryl/alkyl-beta-lactams. A case study.

This article describes an application of the host-guest chiral recognition approach called tweezer methodology for the determination of the absolute configuration of 3-hydroxy-beta-lactams. These substrates represent challenging cases due to their chemical reactivity, the presence of multiple stereogenic centers and several functional groups which offer various possibilities of binding to the Zn-porphyrin host. OPLS-2005, the force field used in this work to predict the interporphyrin twist, modeled correctly the host-guest complexation mechanism and revealed conformational details of the bound substrates.

Synthesis, tubulin assembly, and antiproliferative activity against MCF7 and NCI/ADR-RES cancer cells of 10-O-acetyl-5'-hydroxybutitaxel.

A highly efficient kinetic resolution of racemic cis-4-(2-tert-butyldimethylsilyloxy-1,1-dimethyl)ethyl-3-tert-butyldimethylsilyloxy-azetidin-2-one with 7-O-triethylsilylbaccatin III was carried out to furnish 10-O-acetyl-5'-hydroxybutitaxel after removal of the silyl protecting groups. The compound was 50% as active as paclitaxel in a tubulin assembly assay and showed significantly decreased activity against MCF7 cell proliferation compared to paclitaxel.

Designing new Baeyer-Villiger monooxygenases using restricted CASTing.

This paper outlines the design and execution of the first mini-evolution of cyclopentanone monooxygenase (CPMO). The methodology described is a relatively inexpensive and rapid way to obtain mutant enzymes with the desired characteristics. Several successful mutants with enhanced enantioselectivities were identified.

New bioorganic reagents: evolved cyclohexanone monooxygenase--why is it more selective?

Four mutants of the cyclohexanone monooxygenase (CHMO) evolved as catalysts for Baeyer-Villiger oxidation of 4-hydroxycyclohexanone were investigated as catalysts for a variety of 4-substituted and 4,4-disubstituted cyclohexanones. Several excellent catalytic matches (mutant/substrate) were identified. The most important, however, is the finding that, in a number of cases, a mutant with a single exchange, Phe432Ser, was shown to be as robust and more selective as a catalyst than the wild-type CHMO.

Assignment of absolute configuration of 3-hydroxy beta-lactams by the NMR "mix and shake" method.

The absolute configurations of several 3-hydroxy beta-lactams were assigned by the NMR "mix and shake" methodology developed by Riguera and co-workers. The results from the NMR study correlated perfectly with the absolute configurations obtained from X-ray crystallographic structure analyses and chiral-phase HPLC data.

Access to optically pure 4- and 5-substituted lactones: a case of chemical-biocatalytical cooperation.

Optically pure or highly enantiomerically enriched 4- and 5-substituted lactones are rather difficult to obtain. Chemical or enzymatic syntheses alone are not particularly successful. A combination of chemical catalysis and biocatalysis, however, provides a convenient route to a variety of these useful chiral compounds.

Cloning and characterization of a gene cluster involved in cyclopentanol metabolism in Comamonas sp. strain NCIMB 9872 and biotransformations effected by Escherichia coli-expressed cyclopentanone 1,2-monooxygenase.

Cyclopentanone 1,2-monooxygenase, a flavoprotein produced by Pseudomonas sp. strain NCIMB 9872 upon induction by cyclopentanol or cyclopentanone (M. Griffin and P.

Baker's Yeast-Mediated Reductions of alpha-Keto Esters and an alpha-Keto-beta-Lactam. Two Routes to the Paclitaxel Side Chain.

Baker's yeast (Saccharomyces cerevisiae) has been used to reduce a series of alkyl esters derived from pyruvate and benzoylformate. Both the yield and enantioselectivities of these reductions were maximized when methyl esters were used, and the (R)-alcohols were isolated in all instances. Yeast-mediated ester hydrolysis was a significant side reaction for products derived from long-chain alcohols.