Methanol labeled, synthesis

The epimers of 2-tropanol have been converted into parasympatholytic esters. Molecular complexes of cocaine with thiamine were prepared." labelled (-)-cocaine and -norcocaine were obtained with [ H]methanol. A synthesis of N-C Hs-labelled tropine and atropine from the A-ethoxycarbonyl derivatives was carried out by reduction with lithium aluminium deuteride. 

The literature contains ample evidence that methanol is synthesized from CO2 according to (19) and not from CO as in (18). Isotopic labeling experiments have demonstrated that CO2 is the main source of carbon in methanol formed from synthesis gas [G.C. Chinchen, P.J. Denny, D.G. Parker, M.S. Spencer, K.C. Waugh and D.A. Whan, Appl. Catal. 30 (1987) 333], In addition, it has been shown that a Cu(lOO) single crystal readily produces methanol from a mixture of GO2 and H2 at 2 bar [P.B. Rasmussen, M. Kazuta and I. GhorkendorfF, Suif. Sci. 318 (1994) 267]... 

SCHEME 7.21 Synthesis of a stable quinone methide using rhodium (II) acetate in methanol.84,93 The 13C label is designated with an asterisk ( ). 

Labelled [2H3]dodecyltrimethyl ammonium iodide ([2H3]Ci2TMAI) was synthesised as an internal standard for the quantitative determination of dodecyltrimethyl ammonium chloride (Ci2TMAC) in sewage and river water samples by using FAB-MS [117]. The synthesis of [2H3]Ci2TMAI involved the reaction of dimethylamino dodecane with deuterated methyl iodide (CD3I) in methanol. 

Koichi Fukase et al. reported an example of oligosaccharide synthesis by combining microreactors and an isolation strategy called synthesis based on affinity separation (SAS) [72, 73], The glycosylation was carried out under continuous flow, and the mixture was directly sent to the stainless steel affinity column, and the flow channel was switched to wash the column with CH2C12. The labeled disaccharide was trapped in the column later to be eluted with a mixture of CH2C12 and methanol to obtain the isolated oligosaccharide product. 

To monitor tumor response to capecitabine therapy noninvasively, Zheng and co-workers, from the Indiana University School of Medicine, developed the synthesis of the fluorine- 18-labeled capecitabine as a potential radiotracer for positron emission tomography (PET) imaging of tumors.28 Cytosine (20) was nitrated at the C-5 position with nitric acid in concentrated sulfuric acid at 85°C, followed by neutralization to provide 5-nitrocytosine (27) in moderate yield. This nitro pyrimidine was then carried through the glycosylation and carbamate formation steps, as shown in the Scheme below, to provide the 6/s-protected 5-nitro cytidine 28 in 47% for the three-step process. Precursor 28 was then labeled by nucleophilic substitution with a complex of 18F-labeled potassium fluoride with cryptand Kryptofix 222 in DMSO at 150 °C to provide the fluorine-18-labe led adduct. This intermediate was not isolated, but semi-purified and deprotected with aqueous NaOH in methanol to provide [l8F]-capecitabine in 20-30% radiochemical yield for the 3-mg-scale process. The synthesis time for fluorine-18 labeled capecitabine (including HPLC purification) from end of bombardment to produce KI8F to the final formulation of [18F]-1 for in vivo studies was 60-70 min. 

Chinchen GC, et al. Mechanism of methanol synthesis from CO2/CO/H2 mixtures over copper/zinc oxide/alumina catalysts - use of 14C-labeled reactants. Appl Catal. 1987 30(2) 333-8. 

Carbon-11 labeled BPA, 4, was synthesized from the corresponding aldehyde, 4-boronophenylacetaldehyde, 9. This boronated aldehyde was prepared from commercially available 4-bromophenylacetic acid, 10, in five synthetic steps (Scheme 1). The synthesis was initiated by the borane reduction8 of acid 10 to the 2-(4-boronophenyl)ethyl alcohol, 11. Alcohol 11 was then carefully oxidized9 to aldehyde 12. In the next step, 4-bromophenylacetaldehyde, 12, was refluxed with ethylene glycol in the presence of a catalytic amount ofp-toluenesulfonic acid to obtain the corresponding acetal 13.10 The boronic acid moiety was introduced at the para position of the phenyl ring by the reaction with butyllithium followed by triisopropyl borate" to obtain the 4-bronophenylacetaldehyde ethylene acetal, 14. In the final step of the synthesis, acetal 14 was treated with concentrated hydrochloric acid in methanol as solvent to obtain the desired precursor, 4-boronophenylacetaldehyde, 9, for the synthesis of carbon-11 labeled BPA, 4, Scheme 2. 

Synthesis of Maduramicin Monoamide with 1.6-Hexanediamine (M-C NH-A One gram of tritium-labeled maduramicin (specific activity 23 iCi/gm) was dissolved in 10 mL of toluene with 100 xL of triethylamine. Ethyl chloroformate (100 pL) was diluted in 15 mL of toluene and was added dropwise to the cold maduramicin solution and allowed to stir at 4 C for 30 minutes. A 10 fold molar excess of 1,6-hexanediamine (1.2 gm) was dissolved in 10 mL of toluene and added. After 11/2 hours of reaction at 4 C, ice cold water (4 C) was added to remove salts and clarify the toluene solution. The reaction product was monitored by silica gel thin-layer chromatography and radioactivity. Maduramicin monoamide with 1,6-hexanediamine (M-CgN ) was purified by silica gel column chromatography using a gradient of methanol in ethyl acetate with or without triethylamine as the mobile phase. The product was stored in toluene at 4 C. 

A constant molar radioactivity with increase in carbon number of the products was obtained when C-labeled ethanol or acetaldehyde was added to the syngas fed to a cobalt catalyst. On the other hand, the radioactivity showed a linear increase with carbon number when labeled methyl formate or formic acid was added to the synthesis gas thus, these compounds, like methanol, undergo decomposition to produce labeled CO which participates in the synthesis. 

In principle also the possibility should be considered that CO is dissociated, as in Fischer-Tropsch synthesis of hydrocarbons, and thereafter partially hydrogenated. A metal carbene would then produce, upon addition of H2O, a molecule of methanol. However, one would expect that with a metal like Rh, which can dissociate CO, the isotopically labelled atoms from C 0 would be scrambled with C 0 atoms in the methanol product but this has not been found.With metals which dissociate CO even more reluctantly, like Pd and Cu, this mechanism is even less likely than with Rh. This does not however exclude the possibility that higher alcohols can be formed by H2O addition to a carbene-like intermediate. 

The existence of mannosylated saccharides linked to dolichol via a pyrophosphate was already well established. Studies by Behrens etal. (1973) had shown that rat liver microsomes could catalyse the synthesis of various lipid-linked oUgosaccharides from GDP mannose and dolichol phosphate, among which were some that were soluble in chloroform-methanol-water (1 1 0.3, v/v). These were more polar than dolichol monophosphate derivatives and could be bound to DEAE-cellulose in the presence of the organic solvent. In an ammonium formate gradient (also in the organic solvent) these polyprenyl saccharides eluted at the position of dolichol pyrophosphate derivatives. Waechter et al (1973) independently showed that a similar class of compounds was produced from GDP-[ C]maimose in the presence of microsomes from hen oviduct and that the labelled products... 

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