Synthesis of eupomatilone-6 and assignment of its absolute configuration

[Reaction: see text]. The Zn-mediated Barbier reaction of the biarylaldehyde 8 with crotyl bromide followed by hydroboration and oxidation provided the gamma-butyrolactones 4 and 5. The stereoselective installation of methyl group at C-3 by using LiHMDS and MeI completed the synthesis of racemic eupomatilone-6 (2) and its diastereomer 3. The spectroscopic data of 2 was in full agreement with reported spectra of natural product, thus confirming the revised relative configuration of eupomatilone-6. Similarly, an optically active (3R,4R,5S)-isomer of eupomatilone-6 (23) was prepared in which the aldol reaction with thiazolidinethione as a chiral auxiliary was employed as a key step. On the basis of the spectroscopic data and optical rotation values of 23, the absolute configuration of eupomatilone-6 was proposed.     

Efficient chemoenzymatic synthesis of ADP-D-glycero-beta-D-manno-heptose and a mechanistic study of ADP-L-glycero-D-manno-heptose 6-epimerase

[reaction: see text] A chemoenzymatic synthesis of ADP-D-glycero-beta-D-manno-heptose (ADP-D,D-Hep) is described in which D,D-Hep 7-phosphate is converted to ADP-D,D-Hep by two biosynthetic enzymes. This strategy allows access to the 6'-deuterated analogue, which upon incubation with the epimerase showed complete retention of the isotopic label at the 6'-position. This provides evidence for a direct oxidation mechanism in which the hydride initially transferred to the NADP+ cofactor is subsequently returned to the same carbon in a nonstereospecific manner.     

Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlH, a non-heme iron dioxygenase of Streptomyces avermitilis

The hydroxylase encoded by the ptlH (SAV2991) gene from the pentalenolactone gene cluster of Streptomyces avermitilis was cloned by PCR and expressed in Escherichia coli as an N-terminal His6-tag protein. Incubation of recombinant PtlH with (+/-)-1-deoxypentalenic acid (5) in the presence of Fe(II), alpha-ketoglutarate, and O2 gave (-)-11beta-hydroxy-1-deoxypentalenic acid (8), whose structure and stereochemistry were determined by a combination of 1H, 13C, COSY, HMQC, HMBC, and NOESY NMR. The steady-state kinetic parameters were kcat = 4.2 +/- 0.6 s-1 and Km (5) = 0.57 +/- 0.19 mM. 8 is a new intermediate in the conversion of the sesquiterpene pentalenene (3) to pentalenolactone (1).     

The unambiguous synthesis and NMR assignment of 4-alkoxy and 3-alkylquinazolines

Contrary to a number of reports, alkylations of the privileged 3,4-dihydroquinazoline scaffold provide N3-alkylated products, and not 4-alkoxyquinazolines. To correctly assign the structure, ¹³C NMR shifts of the –Z–CH_n– (Z=O, N) fragment are necessary; resonances in the 45–55 ppm range are indicative of N3-alkylation. Treatment of 3,4-dihydroquinazoline-4-one with p-TsCl afforded the N3-tosylated compound, whose reaction with an amine yielded the corresponding N3-alkyl derivative. A mechanism corroborated by ¹⁵N-labeling involving pyrimidine ring opening and recyclisation is proposed. Finally, the unambiguous preparation of 4-alkoxyquinazolines is described via treatment of 3,4-dihydroquinazoline-4-ones with PCl₅ followed by an alkoxide.     

Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlI, a cytochrome P450 of Streptomyces avermitilis

A gene cluster encoding all of the enzymes for the biosynthesis of the antibiotic pentalenolactone (1) has recently been identified in Streptomyces avermitilis. The biosynthetic gene cluster contains the ptlI (SAV2999) gene which encodes a cytochrome P450 (CYP183A1). PtlI was cloned by PCR and expressed in Escherichia coli as a C-terminal His6-tag protein. Recombinant PtlI bound pentalenene (3) with high affinity (KD = 1.44 +/- 0.14 muM). Incubation of recombinant PtlI with (+/-)-3 in the presence of NADPH, E. coli flavodoxin and flavodoxin reductase, and O2 resulted in conversion to a single enantiomer of pentalen-13-al (7), by stepwise allylic oxidation via pentalen-13-ol (6). The steady-state kinetic parameters for the oxidation of pentalenene (3) to pentalen-13-ol (6) were kcat = 0.503 +/- 0.006 min-1 and Km = 3.33+/-0.62 muM for 3.     

Formation of a 3-phenyl-4-hydroxy-6-chloropyridazine derivative for GC with ECD- and MS-detection and its application to trace analysis

Summary A capillary GC/MS method for the determination of residues of Pyridate-a new herbicide-and its main metabolite, is given. The method is applicable to maize and rape matrices. Because of the rather unusual method of derivative-formation the development of this method is outlined. The detection limit of the method is better than 10 ng/g.

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Herstellung eines 3-Phenyl-4-hydroxy-6-chlorpyridazin-Derivats zur gas-chromatographischen Trennung und zur nachfolgenden Spurenbestimmung mit ECD und MS

Zusammenfassung Eine Kapillar-GC/MS-Methode zur Bestimmung von Rückständen von Pyridate-einem neuen Herbicid-sowie dessen Hauptmetaboliten wird beschrieben. Die Methode ist auf Mais- und Rapsmatrices anwendbar. Aufgrund der ungewöhnlichen Derivatisierung wird die Entwicklung dieser Methode dargestellt. Die Nachweisgrenze ist besser als 10 ng/g.

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Presented at the 8th International Microchemical Symposium, Graz, August 25–30, 1980.     

Synthetic study of a moss-produced oxylipin and its structural revision

The proposed structure for a moss-produced acetylenic oxylipin (10-keto-type structure) was synthesized from a known glycidol derivative by an 11-step sequence involving epoxide ring opening with a terminal acetylene and enzymatic hydrolysis of a methyl ester intermediate. The NMR spectra of the proposed structure was, however, different from those of the natural oxylipin, which prompted us to synthesize its 9-epi-isomer and two diastereomeric 12-keto-type positional isomers. Comparison of the NMR spectra of the three isomers with those of the natural oxylipin indicated that the natural oxylipin was actually a mixture of the two diastereomeric positional isomers.     

An inhibitor of the human UDP-GlcNAc 4-epimerase identified from a uridine-based library: a strategy to inhibit O-linked glycosylation

The biological study of O-linked glycosylation is particularly problematic, as chemical tools to control this modification are lacking. An inhibitor of the UDP-GlcNAc 4-epimerase that synthesizes UDP-GalNAc, the donor initiating O-linked glycosylation, would be a powerful reagent for reversibly inhibiting O-linked glycosylation. We synthesized a 1338 member library of uridine analogs directed to the epimerase by virtue of substrate mimicry. Screening of the library identified an inhibitor with a K(i) value of 11 microM. Tests against related enzymes confirmed the compound's specificity for the UDP-GlcNAc 4-epimerase. Inhibitors of a key step of O-linked glycan biosynthesis can be discovered from a directed library screen. Progeny thereof may be powerful tools for controlling O-linked glycosylation in cells.     

New compound Mg3In4V6O24 and its physicochemical characteristic

Journal of Thermal Analysis and Calorimetry - A new compound of the formula Mg3In4V6O24 belonging to the family M3A4V6O24 [where M?=?metal(II), A?=?metal(III)] was obtained...     

Synthesis of formamidines from 2-amino-3-methylquinazolin-4-one and its 6-nitro derivative

The condensation of 2-amino-3-methylquinazolin-4-one and its 6-nitro derivative with dialkyl-, arylalkyl-, and heterylformamides has given the corresponding formamidines of the quinazolinone series. The details of the compounds synthesized are as follows X, R, R′, yield (%), mp (°C, ethanol), R_f (chloroform-methanol (20:1) Al₂O₃): empirical formula: H, CH₃, CH₃, 77, 238–240, 0.49, C₁₂H₁₄ON₄; H, C₂H₅, C₂H₅, 65, 208–210, 0.96, C₁₄H₁₈ON₄; H, CH₃, C₆H₅, 84, 162–164, 0.54, C₁₇H₁₆ON₄; H, (CH₂)₂O(CH₂)₂, 60, 196–197, 0.43, C₁₄H₁₆O₂N₄; H, (CH₂)₅, 6.6, 196–198, 0.4, C₁₅H₁₈·ON₄; NO₂, CH₃, CH₃, 64. 194–196, 0.83, C₁₂H₁₃O₃N₅; NO₂, C₂H₅, C₂H₅, 37, 142–144, 0.8, C₁₄H₁₇O₃N₅; NO₂; CH₃, C₆H₅, 38, 298, 0.88, C₁₇H₁₅O₃N₅; NO₂, (CH₂)₂O(CH₂)₂, 60, 148–150, 0.7, C₁₄H₁₅O₄N₅. Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 680–684, September–October, 1980.     

Density functional theory study of vibrational spectra and assignment of fundamental vibrational modes of 1-methyl-4-piperidone

The FT-IR and FT-Raman spectra of 1-methyl-4-piperidone was recorded and the observed bands were interpreted with the aid of normal coordinate analysis following a full structure optimization and force field calculation based on the density functional theory (DFT) using the standard B3LYP/6-311G** method and basis set combinations. A very good agreement obtained between the simulated and experimental spectra was established and unambiguous vibrational assignments of various modes were proposed based on the results of potential energy distribution (PED) calculations.     

4-Oxo-3-oxa-6,7-diazabicyclo[3.3.0]oct-6-ene and its isomerization

A product of addition of diazomethane to the double bond of crotonolactone — ¹-pyrazolinolactone — was obtained, and its isomerization to ²-pyrazolino-lactone in dry chloroform in the presence of triethylamine was studied. The structures of the compounds were confirmed by elementary analysis and the IR, UV, and PMR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1610–1612, December, 1977.