Jonathan Grote

Diels-alder cyclization of 2,8,10-undecatrienals as a route to 1,2,3,4,4a,5,6,8a-octahydronaphthalenes

Abstract 2,8,10-Undecatrienals have been found to undergo facile Diels-Alder cyclization upon treatment with alkylaluminum chlorides in methylene chloride at low temperature. The reaction is highly endo-selective. Protected alcohol substituents at the C-4 and C-7 positions are fully accommodated and TBDMS protected alcohols show a strong axial preference. The methodology has been applied to a hydronaphthalenecarboxylic add of possible use in a projected total synthesis of the macrocyclic antitumor antibiotic, chlorothricolide.

Synthesis of novel spirolactams by reaction of fluorescein methyl ester with amines

Abstract A family of previously undescribed fluorescein spirolactams was synthesized by reaction of fluorescein methyl ester with a variety of primary amines. The structure of the non-fluorescent spirolactams was elucidated by NMR spectroscopy and X-ray crystallography.

Pseudomonas cepacia lipase mediated amidation of benzyl esters

Abstract Although lipases have been known for some time as catalysts useful for regioselective transesterification or hydrolysis, studies regarding their use as ester amidation catalysts are limited. We have found that the lipase from Pseudomonas cepacia catalyzes amidation reactions with benzyl esters, producing high yields of amides with a variety of different amines.

The utility of enzymes in generating molecular diversity. Lipase mediated amidation of polybenzyl esters

The feasibility of using lipases, particularly Pseudomonas cepacia, for the synthesis of a diverse molecular library is demonstrated. Twenty-six different compounds were synthesized via lipase-catalyzed reaction of a core diester substrate with several amine partners, resulting in formation of a library of amides which were identified using electrospray mass spectrometry.

Stereoselective Pseudomonas cepacia lipase mediated synthesis of α-hydroxyamides

Abstract A new method for the synthesis of α-hydroxyamides via the Pseudomonas cepacia lipase catalyzed amidation of α-hydroxyesters in non-aqueous media is described. Reactivities of α-hydroxy benzyl esters are excellent, resulting in rapid conversions to good yields of α-hydroxyamides, while ethyl and methyl esters react more slowly, and some hindered esters show no reactivity under the conditions studied. Some benzyl esters react stereoselectively, producing excellent yields of asymmetric α-hydroxyamides.

EFFICIENT FLUORESCEIN SPIROLACTAM AND BIS-SPIROLACTAM SYNTHESIS

Reaction of fluorescein methyl ester at ambient temperature with a variety of amines containing different functional groups afforded a family of spirolactams, the structures of which were verified by MS, NMR, and x-ray crystallography. Bis-spirolactams were prepared by subsequent reaction of an aminospirolactam with another molecule of fluorescein methyl ester.

Regioselective Pseudomonas cepacia lipase mediated amidations of benzyl esters with diamines

Abstract Novel Pseudomonas cepacia catalyzed amidations of benzyl esters demonstrate excellent regioselectivity with both symmetrical and unsymmetrical diamines, producing high yields of easily isolated amide products under mild conditions.

O-(fluoresceinylmethyl)hydroxylamine (OFMHA): a reagent for the preparation of fluorescent O-(fluoresceinylmethyl)oxime (FMO)-steroid conjugates.

The 5 and 6-isomers of O-(fluoresceinylmethyl)hydroxylamine reacted with a representative sample of oxo-steroids (6-oxoestradiol, estrone, norethindrone, cortisol, progesterone, and digitoxin-dialdehyde) to produce O-(fluoresceinylmethyl)oxime conjugates in a single step in 24-84% yield after preparative high performance liquid chromotography.

Development of an Abbott ARCHITECT cyclosporine immunoassay without metabolite cross-reactivity

OBJECTIVE We investigated the mechanism by which the ARCHITECT cyclosporine (CsA) chemiluminescent microparticle immunoassay (CMIA) eliminates cross-reactivity to CsA metabolites AM1 and AM9, despite its use of a monoclonal antibody which shows cross-reactivity in fluorescence polarization immunoassays. DESIGN AND METHODS The CMIA was accomplished by incubating an extracted blood sample with magnetic microparticles coated with a very low amount of anti-CsA antibody. After a wash step the microparticles were incubated with a chemiluminescent CsA tracer, followed by a second wash step and measurement of chemiluminescence. The reagent concentrations of salt and detergent were optimized to maximize CsA binding and minimize metabolite interference. RESULTS Elimination of CsA metabolite cross-reactivity was shown using purified metabolites and blood samples containing native CsA metabolites. The CMIA demonstrated precision and sensitivity acceptable for use in a clinical setting. CONCLUSION We conclude that it is possible to eliminate CsA metabolite immuno-cross-reactivity by careful assay design.

Use of lipase for regioselective one pot amidation and hydrolysis

A study of the reactivity of esters with oxygenated linkers in lipase catalyzed transformations demonstrates that enhanced reactivity is observed in amidation reactions, but diminished reactivity is observed in hydrolyses using the same lipase. Two regioselective transformations (amidation and hydrolysis) can thus be achieved with diesters in the same pot using a single catalyst, effectively demonstrating lipases versatility.