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Direct Precursor (direct + precursor)
Selected AbstractsA Stereoselective Formal Synthesis of (,)-FumagillolEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2004Olivier Bedel Abstract A novel formal synthesis of fumagillol, a direct precursor of the antiangiogenic sesquiterpene fumagillin, is described. The main features of the synthesis are a stereoselective Claisen,Ireland rearrangement, a ring-closing metathesis, a chemo- and stereoselective dihydroxylation, and a Julia,Kocienski olefination. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] A Concise and Efficient Synthesis of seco -Duocarmycin SAEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2003Lutz F. Tietze Abstract A short and efficient synthesis of seco -duocarmycin SA (3), a highly potent cytostatic agent and direct precursor of the natural product duocarmycin SA (1), has been achieved. Starting from commercially available 2-methoxy-4-nitroaniline (4) the synthetic protocol contains a Fischer indole synthesis to introduce the heterocyclic scaffold and a radical 5- exo - trig cyclization to furnish the (chloromethyl)indoline ring system as key reactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Characterization of boldione and its metabolites in human urine by liquid chromatography/electrospray ionization mass spectrometry and gas chromatography/mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 1 2006Yunje Kim Boldione (1,4-androstadiene-3,17-dione) is a direct precursor (prohormone) to the anabolic steroid boldenone (1,4-androstadiene-17,-ol-3-one). It is advertised as a highly anabolic/androgenic compound promoting muscularity, enhancing strength and overall physical performance, and is available on the Internet and in health stores. This work was undertaken to determine and characterize boldione and its metabolites in human urine, using both liquid chromatography with electrospray ionization mass spectrometry and gas chromatography with mass spectrometry and derivatization. Boldione and its three metabolites were detected in dosed human urine after dosing a healthy volunteer with 100,mg boldione. The excretion studies showed that boldione and its metabolites were detectable in urine for 48,h after oral administration, with maximum excretion rates after 1.8 and 3.6,h (boldenone case). The amounts of boldione and boldenone excreted in urine from this 100,mg dose were 34.45 and 15.95,mg, respectively. Copyright © 2005 John Wiley & Sons, Ltd. [source] Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith,Lemli,Opitz syndromeANNALS OF HUMAN GENETICS, Issue 3 2001P. E. JIRA Smith,Lemli,Opitz syndrome (SLOS) is caused by mutations in the DHCR7 gene leading to deficient activity of 7-dehydrocholesterol reductase (DHCR7; EC 1.3.1.21), the final enzyme of the cholesterol biosynthetic pathway, resulting in low cholesterol and high concentrations of its direct precursor 7-dehydrocholesterol in plasma and tissues. We here report mutations identified in the DHCR7 gene of 13 children diagnosed with SLOS by clinical and biochemical criteria. We found a high frequency of the previously described IVS8,1 G > C splice acceptor site mutation (two homozygotes, eight compound heterozygotes). In addition, 13 missense mutations and one splice acceptor mutation were detected in eleven patients with a mild to moderate SLOS-phenotype. The mutations include three novel missense mutations (W182L, C183Y, F255L) and one novel splice acceptor site mutation (IVS8,1 G > T). Two patients, homozygous for the IVS8,1 G > C mutation, presented with a severe clinical phenotype and died shortly after birth. Seven patients with a mild to moderate SLOS-phenotype disclosed compound heterozygosity of the IVS8,1 G > C mutation in combination with different novel and known missense mutations. [source] Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the mevalonate pathway in Saccharomyces cerevisiaeBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2010Mohammad A. Asadollahi Abstract The mevalonate pathway in the yeast Saccharomyces cerevisiae was deregulated in order to enhance the intracellular pool of farnesyl diphosphate (FPP), the direct precursor for the biosynthesis of sesquiterpenes. Over-expression of the catalytic domain of HMG1, both from the genome and plasmid, resulted in higher production of cubebol, a plant originating sesquiterpene, and increased squalene accumulation. Down-regulation of ERG9 by replacing its native promoter with the regulatable MET3 promoter, enhanced cubebol titers but simultaneous over-expression of tHMG1 and repression of ERG9 did not further improve cubebol production. Furtheremore, the concentrations of squalene and ergosterol were measured in the engineered strains. Unexpectedly, significant accumulation of squalene and restoring the ergosterol biosynthesis were observed in the ERG9 repressed strains transformed with the plasmids harboring cubebol synthase gene. This could be explained by a toxicity effect of cubebol, possibly resulting in higher transcription levels for the genes under control of MET3 promoter, which could lead to accumulation of squalene and ergosterol. Biotechnol. Bioeng. 2010; 106: 86,96. © 2010 Wiley Periodicals, Inc. [source] Origin of Diastereoselectivity in the Organolanthanide-Mediated Intramolecular Hydroamination/Cyclisation of Aminodienes: A Computational Exploration of Constrained Geometry CGC,Ln Catalysts,CHEMISTRY - A EUROPEAN JOURNAL, Issue 32 2007Sven Tobisch Dr. Abstract The regulation of ring-substituent diastereoselectivity in the intramolecular hydroamination/cyclisation (IHC) of ,-substituted aminodienes by constrained geometry CGC,lanthanide catalysts (CGC=[Me2Si(,5 -Me4C5)(tBuN)]2,) has been elucidated by means of a reliable DFT method. The first survey of relevant elementary steps for the 1-methyl-(4E,6)-heptadienylamine substrate (1) and the [{Me2Si(,5 -Me4C5)(tBuN)}Sm{N(TMS)2}] starting material (2) identified the following general mechanistic aspects of Ln-catalysed aminodiene IHC. The substrate-adduct 3 -S of the active CGC,Ln,amidodiene compound represents the catalyst's resting state, but the substrate-free form 3, with a chelating amidodiene functionality is the direct precursor for cyclisation. This step proceeds with almost complete regioselectivity through exocyclic ring closure by means of a frontal trajectory, giving rise to the CGC,Ln,azacycle intermediate 4. Subsequent protonolysis of 4 is turnover limiting, whilst the ring-substituent diastereoselectivity is dictated by exocyclic ring closure. Unfavourable close interatomic contacts between the substrate's ,-substituent and the catalyst backbone have been shown to largely govern the trans/cis selectivity. Substituents of sufficient bulk in the ,-position of the substrate have been identified as being vital for stereochemical induction. The present study has indicated that the diastereoselectivity of ring closure can be considerably modulated. The variation of the lanthanide's ionic radius and introduction of extra steric pressure at the substrate's ,-position and/or the CGC N centre have been identified as effective handles for tuning the selectivity. The quantification of these factors reported herein represents the first step toward the rational design of improved CGC,Ln catalyst architectures and will thus aid this process. [source] | |||||||||||||