ABSTRACT
[structure] Enantiomerically enriched trans-chlorocyclopropanemethanol was obtained by lipase kinetic resolution of dichlorocyclopropanemethanol 3, followed by reduction. The sp-sp(2) bond of the trans-chlorocyclopropane dienyne side chain of callipeltoside A was constructed via a Stille coupling reaction of 1, 1-dibromo-1-alkene 7 and a vinylstannane in a highly dipolar solvent capable of promoting HBr elimination to give internal alkynes.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-HIV Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Cyclopropanes/chemical synthesis , Macrolides , Animals , Catalysis , Hydrobromic Acid , Lipase/chemistry , Magnetic Resonance Spectroscopy , Palladium , Porifera/chemistry , Solvents , Stereoisomerism , Tin Compounds/chemistry , Vinyl Compounds/chemistryABSTRACT
[reaction: see text] The C1-C9 fragment of callipeltoside (17) was prepared in 12 steps and 7.2% overall yield from bicyclic lactone (+)-4. Key steps include a stereoselective epoxidation and further regiocontrolled nucleophilic opening of the oxirane ring to install two vicinal stereocenters (C5 and C6), and the use of bis(trimethylsilyl) peroxide and a catalytic amount of Sn(IV) chloride for the chemoselective Baeyer-Villiger oxidation of unsaturated cyclopentanone 15.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Biochemistry/methods , MacrolidesABSTRACT
2-Methoxynaphthalene was subjected to biooxidation by whole cells of six organisms: Pseudomonas putida F39/D containing toluene dioxygenase, Escherichia coli JM109(pDTG601), containing recombinant toluene dioxygenase from Pp F39/D, Pseudomonas sp. NCIB 9816/11, containing naphthalene dioxygenase. E. coli JM109(pDTG141), containing recombinant naphthalene dioxygenase from NCIB 98161/11, E. coli C534(ProR/Sac) containing recombinant naphthalene dioxygenase from Pp G7, and Beijerinckia sp. B8/36, containing biphenyl dioxygenase. The major product of oxidation by the naphthalene and biphenyl dioxygenases has been isolated and identified as (1R,2S)-dihydroxy-7-methoxy-1,2-dihydronaphthalene, 2c. A minor product, (1R,2S)-dihydroxy-6-methoxy-1,2-dihydronaphthalene, 3c, has also been detected. Oxidation by the toluene dioxygenase-containing organisms led to the isolation of 3c as the major product. Minor products detected in these reactions were 2c, and a third compound, (1S,2S)-dihydroxy-3-methoxy-1,2-dihydronaphthalene, 4c. Structural studies and dehydration of the diols to a mixture of naphthols are described. The absolute stereochemistry of these new diols has been established by correlation with known compounds. The organisms' potential in the production of new metabolites as useful chiral synthons by biooxidation of 2-substituted naphthalenes is indicated.
Subject(s)
Naphthalenes/metabolism , Oxazines/chemistry , Oxygenases , Bacteria/enzymology , Dioxygenases , Escherichia coli/enzymology , Magnetic Resonance Spectroscopy , Molecular Structure , Multienzyme Complexes/metabolism , Optical Rotation , Oxazines/isolation & purification , Oxidation-Reduction , Oxygenases/metabolism , Pseudomonas/enzymology , Pseudomonas putida/enzymology , Recombinant Proteins/metabolism , StereoisomerismABSTRACT
The endo-hydroxylactone (+/-)-(1) was resolved by enantioselective acetylation using Candida cylindracea lipase or preferentially Pseudomonas fluorescens lipase (pfl). Alternatively the corresponding butyrate (+/-)-(3) was hydrolysed with pfl to give the ester (+)-(1S,4R,5S)-(3) and the alcohol (-)-(1R,4S,5R)-(1). The latter compound was converted into carbovir (-)-(1R,4S)-(12) while the ester (+)-(3) was transformed into the delta-lactone (+)-(3R,5S)-(18). The exo-hydroxylactone (+/-)-(2) was resolved less efficiently by a trans-esterification process employing pfl and vinyl acetate.
