Biosynthese de la botryodiplodine,mycotoxine de penicillium roqueforti: Incorporations d'acetate[1-13C], [2-13C], [1-2 13C]et d'acide orsellinique 2-13C-carboxyle 13C], [3-4 13C]

Incorporations of [1-¹³C], [2-¹³C], [1-2¹³C]acetate and [2-¹³C, carboxyl-¹³C], [3-4¹³C]orsellinic acid into botryodiplodin indicate that this mycotoxin is biosynthesized by the polyketide pathway. Orsellinic acid is a precursor of botryodiplodin. A biosynthetic pathway, using orsellinic acid as precursor, is proposed.     

13C?13C spin coupling constants in tetrahydronaphthylene,hexahydrobenzanthracene and benzo[a]pyrene derivatives

The ¹³C? ¹³C spin coupling constants have been determined in substituted [1-¹³C]tetrahydronaphthylenes, [5-¹³C]hexahydrobenzanthracenes and [5-¹³C]benzanthracene. In addition, the ¹³C? ¹³C spin coupling constants for 7-hydroxy[7-¹³C]benzopyrene, trans-7,8-dihydro[7-¹³C]benzopyrene-7,8-diol and trans-7,8-dihydro[10-¹³C]benzopyrene-7,8-diol are reported, together with the one-bond carbon-carbon coupling constants between C-4 and C-5 in selected 4,5-disubstituted benzopyrenes. Values for the directly bonded coupling constants and long-range coupling constants are similar to those reported previously for other aromatic and aliphatic systems. Substituent effects on carbon-carbon coupling are compared for similarly substituted cyclic and acyclic systems.     

Synthesis of [1-15N,2-13C]-labeled difloxacin

Abstract  

The synthesis of [1-¹⁵N,2-¹³C]-difloxacin, an arylfluoroquinolone antibacterial agent, is reported. As a crucial initial step, the starting materials ethyl 2,4,5-trifluorobenzoylacetate, [formyl-¹³C]-triethyl orthoformate, and [¹⁵N]-4-fluoroaniline were reacted to ethyl [¹⁵N,3-¹³C]-3-(4-fluoroanilino)-2-(2,4,5-trifluorobenzoyl)acrylate. After cyclization and ester cleavage, the resulting intermediate was reacted with 1-methylpiperazine to [1-¹⁵N,2-¹³C]-1-(4-fluorophenyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate, i.e., [1-¹⁵N,2-¹³C]-difloxacin. The overall yield was 62% based on the non-labeled and 43% based on the labeled starting materials (both used in 1.4 molar excess). The product was identified by ¹H-, ¹³C-, and ¹⁵N-NMR spectroscopy and by cochromatography (TLC, HPLC) with an authentic reference; its purity (HPLC) was above 98%. Prior to synthesis of [1-¹⁵N,2-¹³C]-difloxacin, non-labeled difloxacin was synthesized in order to optimize procedures and to identify and characterize all intermediates.     

Biosynthesis of kinamycin D. incorporation of [1,2-13C] acetate and of [2-2H3,1-13C]acetate

Results from the incorporation of [1,2-¹³C₂]- and [2-²H₃,1-¹³C]acetates into kinamycin D. indicate the involvement of only unsymmetrical intermediates; the identity of some of these are suggested.     

Biosynthesis of psilotin from [2′,3′-13C2,1′-14C,4-3H]phenylalanine studied with 13C-NMR

The 6-phenyl-dihydro-α-pyrone moiety of psilotin is formed from [2′,3′-¹³C₂,1′-¹⁴C,-4-³H]phenylalanine in the plant $\text{Psilotum}$$\text{nudum}$ with retention of all the isotopes.     

Deuterium-induced 13C NMR isotope shifts for signal assignments and determination of deuteriation site in cyclododecanone

Deuterium-induced ¹³C isotope shifts were measured in the ¹³C {¹H} NMR spectra of monodeuteriated cyclododecanones formed upon oxidation of [1-²H₁] cyclododecanol with lead tetraacetate. These shifts, when used in conjunction with ¹³C NMR data of specifically labelled analogues, [2, 2, 12, 12-²H₄]- and [2-²H₁] cyclododecanone, enabled the ketone formed with lead tetraacetate to be identified as a mixture of [5-²H₁]- and [6-²H₁] isotopomers.     

13C NMR spectrum of coumarin

Summary The positions of the signals from the C₃, C₅, C₆, and C₇ carbon atoms in the¹³C NMR spectrum of coumarin have been established with the aid of information obtained from the¹³C NMR spectra of [3-D]-, [4-D]-, and 7-methoxycoumarins and by the use of an additive calculation based on the increments of the methoxy group in the¹³C NMR spectrum of anisole.M. V. Lomonosov Moscow State University Scientific-Research Institute of Pharmacology, Academy of Medical Sciences of the USSR. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 458–462, July–August, 1975.     

The mass spectra of [17-13C]phyllocladene and [3-13C]methylenecholestane—III

The mass spectra of [17-¹³C]phyllocladene and [3-¹³C]methylenecholestane have been examined. It is shown that there are some rearrangements at 70 e V as in the case of [17-¹³C]kaurene. However, no extensive randomization is evident at the molecular ion level. The results are interesting because very little is known about ¹³C randomization in polycyclic aliphatic hydrocarbons. The percentage retention of label was calculated for each ion.     

Synthesis of dl-[2-13C]leucine and it use in the preparation of [3-dl-[2-13C]leucine]oxytocin and [8-dl-[2-13C]leucine]oxytocin: Preparative separation of diastereoisomeric peptides by partition chromatography and high pressure liquid chromatography

dl-[2-¹³C]Leucine was prepared by condensing the sodium salt of ethyl acetamido-[2-¹³C]cyanoacetate with isobutylbromide in hexamethylphosphoroustriamide followed by acid hydrolysis. N-Boc-dl-[2-¹³C]Leucine was prepared and incorporated into [8-dl-[2-¹³C]leucine]oxytocin by total synthesis. The ¹³C-labeled hormone derivative [8-[2-¹³C]leucine]oxytocin was separated from its 8-position diastereoisomer by partition chromatography. The specifically ¹³C-labeled peptide hormone diastereoisomeric analog [3-dl-[2-¹³C]leucine]oxytocin also was prepared by solid phase peptide synthesis. No suitable solvent system for partition chromatography separation of the latter diastereoisomeric peptide mixture could be found. However an excellent preparative separation of the diastereoisomers could be obtained by reverse phase high pressure liquid chromatography on a partisil 10 M9 ODS column using the solvent system 0.05 M ammonium acetate (pH 4.0), acetonitrile (81:19, $\text{v}\text{v}$) to give pure [3-(2-¹³C]leucine]oxytocin and [3-D-(2-¹³C]leucine]oxytocin. An excellent separation of [8[2-¹³C]leucine]oxytocin and the corresponding 8-D-leucine diastereoisomer derivative could also be accomplished by high pressure liquid chromatography.     

The conformational dependence of 15n13c spin spin coupling constants

2-Azabicyclo(2.2.2)octan-3-One 1, N-isopropylpivaloylamide 2 and 4-azatricyclo(4.3.1.1^3,8)undecan-5-one 3 have been prepared with a ¹⁵N label. The amides were reduced to the corresponding amines 2-azabicy-clo(2.2.2)octane 4, N-isopropyl-N-neopentylamine 5 and 4-azatricyclo(4.3.1.1^3,8)undecane 6. The ¹³C spectra of these compounds and their hydrochlorides were measured and the ¹⁵N¹³C spin coupling constants interpreted in terms of their conformational dependence.     

13C-NMR-spektren stereoisomerer 1,4-dialkylspiro[4.5]decan-derivate

The ¹³C NMR spectra of a series of 7-substituted 1,4-dialkylspiro[4.5]decanes and of suitable reference compounds are assigned and the derived substituent effects upon the chemical shifts are discussed. In particular, consideration of γ and δ-effects allows the differentiation between 1,4-cis- and 1,4-trans-compounds. Furthermore, the (relative) configuration of the chiral spiroatom C-5 is determined.     

An asymmetric synthesis of l-[3-C]phenylalanine and l-[3-C]tyrosine from [C]carbon monoxide

-[3-¹³C]Phenylalanine and -[3-¹³C]tyrosine were synthesized. [α-¹³C]Benzyl bromides were prepared from [¹³C]carbon monoxide via the palladium-catalyzed carboalkoxylation of aryl halides. The asymmetric carbon corresponding to the 2-position in phenylalanine was introduced by the diastereoselective alkylation of Dellaria's oxazinone with [α-¹³C]benzyl bromides. Finally, ethanolysis, deprotection, hydrogenolysis and acid hydrolysis of the resulting alkylated oxazinones gave -[3-¹³C]phenylalanine and -[3-¹³C]tyrosine in high optical purity.     

Simple NMR method for assigning relative stereochemistry of bridged bicyclo[3.n.1]-2-enes and tricyclo[7.n.1.0]-2-enes

The stereochemistry of syn and anti-forms of bridged bicyclo[3.n.1]-2-ene, tricyclo[7.n.1.0]-2-ene (n=1-3) and bicyclo[4.3.1]dec-7-ene derivatives can be assigned from the ¹³C chemical shift difference of the double bond. Both syn-9-R-bicyclo[3.3.1]non-2-enes and syn-13-R-tricyclo[7.3.1.0^2,7]tridec-2(7)-enes have a large shielding difference between sp² carbons, while the corresponding anti-forms have a smaller one. In contrast, 8-R-bicyclo[3.2.1]oct-2-enes and 12-R-tricyclo[7.2.1.0^2,7]dodec-2(7)-enes have an inverse correlation. The reason of this specificity is the influence of the γ-gauche effect on the chemical shift of C(2) atom. The GIAO theory has been applied to investigate the ¹³C chemical shifts. The conformational equilibrium in the formamide group of 13-formylamino-tricyclo[7.3.1.0^2,7]tridec-2(7)-enes has been studied.     

Synthesis of [3,4,8-C3]daidzein

The biological effects of the soy isoflavones have attracted considerable interest in recent years leading to numerous studies on dietary intake and epidemiology. Such studies require accurate and reproducible analytical methods. Herein we report the first synthesis of a multiply ¹³C-labelled daidzein derivative, [3,4,8-¹³C₃]daidzein, which has been employed as an internal standard in LC-MS and GC-MS analysis. The synthesis includes an improved three-step method for the synthesis of [2-¹³C]resorcinol as one building block.     

ParaHydrogen Polarized Ethyl-[1-13C]pyruvate in Water,a Key Substrate for Fostering the PHIP-SAH Approach to Metabolic Imaging

An efficient synthesis of vinyl-[1-¹³C]pyruvate has been reported, from which ¹³C hyperpolarized (HP) ethyl-[1-¹³C]pyruvate has been obtained by means of ParaHydrogen Induced Polarization (PHIP). Due to the intrinsic lability of pyruvate, which leads quickly to degradation of the reaction mixture even under mild reaction conditions, the vinyl-ester has been synthesized through the intermediacy of a more stable ketal derivative. ¹³C and ¹H hyperpolarizations of ethyl-[1-¹³C]pyruvate, hydrogenated using ParaHydrogen, have been compared to those observed on the more widely used allyl-derivative. It has been demonstrated that the spin order transfer from ParaHydrogen protons to ¹³C, is more efficient on the ethyl than on the allyl-esterdue to the larger J-couplings involved. The main requirements needed for the biological application of this HP product have been met, i. e. an aqueous solution of the product at high concentration (40 mM) with a good ¹³C polarization level (4.8 %) has been obtained. The in vitro metabolic transformation of the HP ethyl-[1-¹³C]pyruvate, catalyzed by an esterase, has been observed. This substrate appears to be a good candidate for in vivo metabolic investigations using PHIP hyperpolarized probes.     

An Efficient Synthesis of Optically Active [4-13C] Labelled Quorum Sensing Signal Autoinducer-2

A new synthetic route for the quorum sensing signal Autoinducer-2 (AI-2) is described and used for the preparation of [4-¹³C]-AI-2 starting from [1-¹³C]-bromoacetic acid. The key step in this process was the enantioselective reduction of an intermediate ketone. This synthesis provides, selectively, both enantiomers of the labelled or unlabelled parent compound, (R) or (S)-4,5-dihydroxypentane-2,3-dione (DPD) and was used for an improved synthesis of [1-¹³C]-AI-2.     

Microwave spectra of tetrahydroselenophene-α13C, -β13C and molecular ring structure

Microwave spectra of isotopic species α-¹³C and β-¹³C of tetrahydroselenophene molecules have been investigated and rotational constants determined: A = 5608.98 Mc, B = 2819.532 Mc, C = 2022.624 Mc forα-¹³C isotopic species and A = 5695.94 Mc, B = 2770.714 Mc, C = 2009.166 Mc for β-¹³C isotopic species. The r_s-ring structure was found to be Se-C₂ = 1.963 Å, C₂-C₃ = 1.549 Å, C₃-C₄ = 1.527 Å, ∠C₅SeC₂ = 90° 44', ∠SeC₂C₃ = 104° 58', ∠C₂C₃C₄ = 106° 52', the angle of twist = 29° 44'.     

Carbon-13 nuclear magnetic resonance spectra of some mesoionic xanthine analogs

Natural abundance ¹³C NMR chemical shifts have been experimentally determined for a series of mesoionic thiazolo[3,2-a]pyrimidine-5,7-diones. The spectral data are compared with those of related mesoionic dihydrothiazolo[3,2-a]pyrimidine-5,7-diones and mesoionic 1,3,4-thiadiazolo[3,2-a]pyrimidine-5,7-diones. Resonable correlation between the observed ¹³C NMR chemical shifts and CNDO/2 total charge densities have been obtained for the different carbon atoms of 8-methylthiazolo[3,2-a]pyrimidine-5,7-dione.     

Zum Mechanismus der α-Alkinon-Cyclisierung: Synthese und Thermolyse von 1-(1-Methylcyclopentyl)[3-13C]prop-2-inon

On the Mechanism of the α-Alkynone Cyclization: Synthesis and Thermolysis of 1-(1-Methylcyclopentyl)[3-¹³C]prop-2-ynone The relative migratory aptitude of two acetylenic substituents in the α-alkynone cyclization, a thermal conversion of α-acetylenic ketones A to 2-cyclopentenones C , was investigated by isotope-labeling experiments. The α-alkynone [β-¹³C]- 1 , specifically labeled with ¹³C at the β-acetylenic C-atom C(3), was synthesized by an intramolecular Witting reaction (230–300°) of the diacylmethylidenephosphorane [¹³C]- 7. The latter resulted from acylation of methylidenetriphenylphosphorane with the acid chloride 4 to yield the acylmethylidenephosphorane 5 , which in turn was formylated with acetic [¹³C]formic anhydride ([¹³C]- 6. ) Upon thermolysis of [β-¹³C]- 1 , its label at C(β) was transferred almost exclusively to C(β) of the 2-cyclopentenone moiety in the resulting cyclization product [¹³C]- 2. We conclude that there is a distinct preference for hydrogen migration in the acetylene → alkylidene carbene isomerization (A → B) which precedes the cyclization step (B → C). No evidence was found for a fast reversibility of this isomerization (A ? B) involving both acetylenic substituents.     

Biosynthesis of highly modified meroterpenoids in aspergillus variecolor. Incorporation of 13C-labelled acetates and methionine into anditomin and andilesin C

Incorporations of [1-¹³C]?, [2-¹³C]?, [1,2-¹³C₂]-acetates and [¹³C]-methionine into anditomin, a metabolite of $\text{Aspergillus variecolor}$, indicate its formation by a mixed polyketide-terpenoid biosynthetic pathway similar to that elucidated for andibenin; observations are made on the possible biosynthetic relationship of the $\text{A. variecolor}$ metabolites with austin and terretonin, mycotoxins recently isolated from $\text{A. ustus}$ and $\text{A. terreus}$ respectively.