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.     

Unequivocal assignment of the δ resonances of 2-substituted adamantanes by two-dimensional inadequate 13C NMR spectroscopy

Two-dimensional INADEQUATE NMR spectroscopy was used to assign unequivocally the $\text{syn}$ and $\text{anti}$ δ ¹³C resonances of 2-substituted adamantanes.     

The structure of azadirachtin and 22,23-dihydro-23β-methoxyazadirachtin

On the basis of NMR data including NOE experiments, ¹³C deuterium isotope shifts, and ¹³C-¹H long range coupling we suggest structure $\text{2}$ and $\text{3}$ for azadirachtin, and 22,23-dihydro-23β-methoxyazadirachtin, resp.     

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.     

Synthesis of 13C and 15N labelled (S)-Tryptophan

(R,S)-serine-1-¹³C was incubated in a culture of $\text{Escherichia}$$\text{coli}$ cells to produce (S)-trytophan-1-¹³C. Bromoacetyl bromide-2-¹³C was converted to bromoacetanilide and cyclization of the anilide, followed by reduction and dehydrogenation furnished indole-3-¹³C. Indole-¹⁵N was synthesized by known sequences. These ¹³C and ¹⁵N isotomers of indole were converted by commercially available, lyophilized $\text{E}$. $\text{coli}$ to furnish (S)-tryptophan-γ-¹³C and (S)-tryptophan-indole-¹⁵N, respectively.     

Synthesis and NMR spectroscopy of 2′, 3′, 4′, 5′, 6′ - pentafluoroformanilide

Pentafluoroformanilide was prepared by a new synthetical route. The ¹H, ¹³C, and ¹⁹F chemical shifts for the compound indicated the presence of $\text{cis}$ and $\text{trans}$ isomers in chloroform with a rotational energy barrier of 13.4 Kcal mol^-1 for the N-C(O) bond.N, N′-Bis(2,3,4,5,6-pentafluorophenyl) formamidine was obtained from pentafluoroformanilide.     

X-ray structure and dynamic behaviour in solution of N-methylthio-N'-2,6-dimethylphenyl).2,6-dimethyl-1,4-quinonediimine formed by the alcoholysis of [Me2 Al{2,6-Me2C6H3NS(Me)NC6H3Me2-2,6}]2

Reaction of [Me₂Al{RNS(Me)NR}]₂ (R = 2,6-Me₂C₆H₃) with t-BuOH affords N-methylthio-N-(2,6-dimethylphenyl)-2,6-dimethyl-1,4-quinonediimine in 67% yield. The X-ray structure of this compound shows that two conformational isomers are present in the solid. Temperature dependent ¹³C and ¹H NMR measurements show that in solution these conformers exchange at a rate which is fast on the NMR time scale at + 60°C and slow at ?₆₀°C. From the coalescence point of two of the ¹³C resonances, the free energy of activation is estimated to be 13.7 + 1.0 $\text{kcal}\text{mol}$ at 10°C. Possible processes for the exchange are discussed, and also a reaction scheme for the formation of the title compound is discussed.     

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.     

Enamine chemistry-XXVI: The [4 + 2] cycloaddition reactions of 3-amino-1-(4-nitrophenyl)-prop-2-ene-1-thione with electrophilic olefins and acetylenes

Enamino-thiones 1 prepared from the corresponding enaminones by thiation with Lawesson's Reagent, were allowed to react with 2-chloroacrylonitrile and dimethyl acetylenedicarboxylate giving dihydro-2$\text{H}$-thiopyrans, 2, and 4$\text{H}$-thipyrans, 3, respectively. The reaction of 1a with ethyl propiolate at room temperature afforded 4$\text{H}$-thipyrans, 4a, which on standing rearranged to 2$\text{H}$-thiopyran, 5a(1, 3 amide shift). The reaction of 1b with ethyl propiolate produced 4b and 5b. Some of the ¹³C NMR data are reported.     

Cycloaddition reactions of 1,3-benzothiazines—I. : Reactions of 2-phenyl-4-H and 4-phenyl-2H-1,3-benzothiazine derivatives with substituted acetyl chlorides

6,7-Dimethoxy-2-phenyl-4$\text{H}$-1,3-benzothiazine (1) and 6,7-dimethoxy-4-phenyl-2$\text{H}$-1,3-benzothiazine (2) react with substituted acetyl chlorides to give linearly, and new angularly condensed β-lactam derivatives (4,5). Heating of the latter compounds with hydrogen chloride in anhydrous ethanol leads to the formation of the corresponding 4$\text{H}$- and 2$\text{H}$-1,3-benzothiazinium chloride, respectively. The configurations of these compounds (the mutual positions of the substituents relative to the β-lactam ring) were determined by ¹H and ¹³C studies, also making use of the aromatic solvent-induced shifts.     

Generalite de l'effet structural d'un motif bitertiaire en rmn 13C: effet gem-6 de 6ème substitution methyle

In di-tertiary groups like (Me₃C)₂¹³C, the sixth methyl substituent $\text{inverts}$ or $\text{attenuates}$ the induced ¹³C chemical shift of sp² or sp³ sites (B_σ and y_π effects).     

Stereochemical studies 83 saturated heterocycles 76 : Preparation and conformational study of partially saturated 3,1-benzoxazines, 3,1-benzoxazin-2-ones and 3,1-benzoxazine-2-thiones

The $\text{cis}$- and $\text{trans}$-2-amino-4-cyclohexene-1-carboxylic acids $\text{1}$ and $\text{3}$ react with imidates to give the condensed-skeleton, bicyclic $\text{cis}$- and $\text{trans}$-pyrimidin-4-ones $\text{8}$ and $\text{9}$. The amino acids $\text{1}$ and $\text{3}$ were reduced to the $\text{cis}$-and $\text{trans}$-1, 3-aminoalcohoIs $\text{6}$ and $\text{7}$, which were cyclized by means of imidates to the bicyclic tetrahydro-4$\text{H}$-3,1-benzoxazines $\text{10}$ and $\text{11}$, or were converted, $\text{via}$ the corresponding carbamates $\text{14}$ and $\text{15}$ into the tetrahydro-4$\text{H}$-3,1-benzoxazin-2(1$\text{H}$)-ones $\text{16}$ and $\text{17}$. The 2-thioxo analogues $\text{18}$ and $\text{19}$ were prepared by cyclization of the dithiocarbamates obtained from the aminoalcohols $\text{6}$ and $\text{7}$ by treatment with carbon disulphide. The $\text{trans}$-aminoalcohol $\text{7}$ and its saturated analogue reacted with $\text{p}$-chlorobenzaldehyde to furnish the hexahydro $\text{13}$ and octahydro-4$\text{H}$-3,1-benzoxazine $\text{13a}$, respectively. ¹H and ¹³C NMR studies showed that, similarly to the earlier-investigated analogues containing oxygen or unsubstituted nitrogen at position 1, the synthesized $\text{cis}$ isomrs $\text{8}$, $\text{10}$, $\text{16}$ and $\text{18}$ occurred as the preferred conformer in the heterocyclic twist inverse form of $\text{N}$-inside type ($\text{quasiaxial}$ C₆-N bond) (B). In the $\text{trans}$ isomers containing a saturated C-2 atom ($\text{13}$ and $\text{13a}$), H-2 and H-6 are in $\text{cis}$ relative positions.     

13C-NMR of some ajmalane alkaloids

The ¹³C-NMR spectra of the alkaloid ajmaline ($\text{1}$) and its stereoisomers isoajmaline ($\text{2}$), sandwichine ($\text{3}$) and isosandwichine ($\text{4}$) are reported. The different stereochemistry at C (17), C(20) and C(21) of the four isomers can be directly ascertained by chemical shifts data.     

Epoxidation with the H2O2/vilsmeier reagent system

Alkenes $\text{1}$ a–d interact at ?80°C in 15 min. with the Vilsmeier reagent $\text{I}$ (Me₂N=CHCl)⁺PO₂Cl₂^? in presence of 30% H₂O₂ to yield the corresponding epoxides $\text{3}$ a–d. The reaction could involve the formation of the highly reactive hydroperoxymethylenedimethylammonium salt (Me₂N=CHOOH)⁺PO₂Cl^?₂$\text{II}$.     

Stereoselective synthesis of 3-(1-Hydroxyethyl)-2-azetidinonesfrom 3-hydroxybutyrates

Addition of dianions of 3-hydroxybutyrates to benzylideneaniline results in direct formation of $\text{trans}$$\text{S*}$-3-(l-hydroxyethyl)-1,4-diphenyl-2-azetidinone with 95% diastereoselectivity. Inversion of the configuration at Cα, gives the desired $\text{trans}$$\text{R*}$-2-azetidinone in high yield.     

Voie d'accès aux amino-3(5) pyrazoles substitués en 4 par un groupement SEt

Reaction of hydrazine with bromoderivatives $\text{1}$, obtained from aldehydes, gives almost quantitatively 3(5)-aminopyrazoles $\text{2}$. An approach of the structure of $\text{2}$ is attempted by ¹³C NMR.     

Easy conjugate additions to Δ1(9)-octal-2-one and its 10-methyl derivative

Conjugate additions of lithiated arylacetonitriles to 2-octalones give good yields of $\text{cis}$-decalone products. The stereochemistry of the adducts is determined by ¹³C NMR spectroscopy.     

Nature of the catalytic cycle in iridium-complex catalysed hydrogenation of unsaturated alcohols

The $\text{endo}$ face specific reduction of $\text{endo}$-6-methylenebicyclo[2,2,2]octan-2-ol and $\text{endo}$-6-methy[bicyclo [2,2,2]-oct-5-en-2-ol with D₂ and iridium catalysts is accompanied by deep-seated isotopic redistribution through an intramolecular mechanism, although only two deuterium atoms are incorporated on average. Individual isotopomers of the product may be identified in the ¹³C N.m.r. spectrum at 125 MHz. and their ratio is generally consistent with a mechanism in which product is formed by breakdown of an alkyliridium trihydride. Iridium (and rhodium) catalysts part-isomerise the exocyclic olefin to its endocyclic isomer $\text{via}$ an Ir-allyl intermediate without incorporation of deuterium. The reduction of 3-methylcyclohex-2-enol is likewise accompanied by considerable scrambling, with isotopic enrichment occurring at C2, C3, C4 and C5 of the product, $\text{trans}$-3-methylcyclohexanol. Deuteration occurs exclusively on the hydroxyl-bearing face of the molecule.