Synthesis of carbon-14 labelled β-keto ester via magnesium ethyl malonate
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The Synthesis and Applications of Isotopically Labelled Compounds 589 APPLICATION OF 0XYG]~I LAR~TJ,~D CARBON DIOXIDEFOR DETAINING I~ARY DIFFUSING CAPACITY. H. Heller, K.-D. Schuster, R. Meister and E. Nanassy Institute of Physiology I, University of Bonn, 5300 Bonn I, FRG. It is well known that the diffusing capacity of carbon monoxide is signifi- cantly greater during hypoxic hypercapnia as well as during ergometer work when compared with normoxic normocapnia at rest. Previously, the diffusing capacity (D) of oxygen labeled CO2, C1802, has been determined in healthy hi, hans at hypoxic hypercapnia and normoxic normocapnia but no difference has been found. The question therefore arises whether D of C1802 increases during engometer work or not. 63 sir~ole breath experiments were performed on 3 humans. The subjects were sitting on a bicycle ergometer, resting or pe- dalling against a work load of 75 W. 10 minutes of pedalling were performed prior to the experiments to reach steady state conditions. During the single breath manoeuvre the subjects inspired a gas mixture containing 0.7% C1802, 20% 02 and balance nitrogen. Breath-hold times ranged from 0.5 to 20 s. End- expired gas was collected and anal]rsed by mass spectrometry. The C1802 diffusing capacities of the three subjects given in ml mmHg-I min-I , range from 781 to 1268 during rest and 960 to 1837 during engometer work, respec- tively.The ratios Dwork/Drest are between 1.23 d 0.09 and 1.63 ± O.12 (P = 0.05). These results together with an analysis of data from literature sug- gest:(1) an important factor to increase single breath CO diffusing capacity during hypoxic hypercapnia is considered to be an accelerated reaction ki- netics of carbon monoxide in blood, (2) the increase of single breath C1802 diffusing capacity during engometer work indicates improvements of the dif- fusing conditions of the lungs which were likely brought about by recruit- ment or distension of lung capillaries, (3) when partitioning CO2 transfer between capillary blood and alveolar gas into a diffusing conductance (DM) and a blood conductance (SVc), C02 transfer is limited to 13-19 % by DM and to 81-89 % by 9Vc during rest as well as during work load of 75 W. SYNTHESIS OF CARBON-14 LABELED ~-KETO ESTERVIA MAGNESIUMETHYL MALONATE H. Lee, P. Woo, L. Santay, A. Travalent, H. Roark, T. Capiris, and C.C. Huan~ Chemistry Department Parke-Davis Pharmaceutical Research Division Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI 48105 USA ~-Keto esters are versatile common intermediates for the synthesis of many types of pharmaceuticals. However, currently available methods of incorporating a radiolabel into a ~-keto ester oftentimes do not give reproducible and satisfactory results. A facile method using magnesium ethyl malonate based on modifications of the work of Bram and Vilkas (Bull. Soc. Chim., 945 (1964)) was developed for the synthesis of labeled ~-keto esters. For example, heating of magnesium ethyl malonate with labeled 1-[ C]acetylimidazole followed by acid hydT~lysis/decarboxylation gave a quantitative yield of ethyl [3-~C]acetoacetate. The method has also been applied to the synthesis of other labeled and unlabeled ~-keto esters with excellent results. O H ~N ~ . ~ 0 ,''Mg ~ R CH2COOEt 0 0 OEt
Transcript of Synthesis of carbon-14 labelled β-keto ester via magnesium ethyl malonate
The Synthesis and Applications of Isotopically Labelled Compounds 589
APPLICATION OF 0XYG]~I LAR~TJ,~D CARBON DIOXIDEFOR DETAINING I~ARY DIFFUSING CAPACITY. H. Heller, K.-D. Schuster, R. Meister and E. Nanassy
Institute of Physiology I, University of Bonn, 5300 Bonn I, FRG.
It is well known that the diffusing capacity of carbon monoxide is signifi- cantly greater during hypoxic hypercapnia as well as during ergometer work
when compared with normoxic normocapnia at rest. Previously, the diffusing
capacity (D) of oxygen labeled CO2, C1802, has been determined in healthy
hi, hans at hypoxic hypercapnia and normoxic normocapnia but no difference has been found. The question therefore arises whether D of C1802 increases during engometer work or not. 63 sir~ole breath experiments were performed on
3 humans. The subjects were sitting on a bicycle ergometer, resting or pe-
dalling against a work load of 75 W. 10 minutes of pedalling were performed prior to the experiments to reach steady state conditions. During the single
breath manoeuvre the subjects inspired a gas mixture containing 0.7% C1802,
20% 02 and balance nitrogen. Breath-hold times ranged from 0.5 to 20 s. End-
expired gas was collected and anal]rsed by mass spectrometry. The C1802 diffusing capacities of the three subjects given in ml mmHg -I min -I , range
from 781 to 1268 during rest and 960 to 1837 during engometer work, respec- tively.The ratios Dwork/Drest are between 1.23 d 0.09 and 1.63 ± O.12 (P =
0.05). These results together with an analysis of data from literature sug-
gest:(1) an important factor to increase single breath CO diffusing capacity
during hypoxic hypercapnia is considered to be an accelerated reaction ki-
netics of carbon monoxide in blood, (2) the increase of single breath C1802 diffusing capacity during engometer work indicates improvements of the dif-
fusing conditions of the lungs which were likely brought about by recruit-
ment or distension of lung capillaries, (3) when partitioning CO 2 transfer between capillary blood and alveolar gas into a diffusing conductance (DM) and a blood conductance (SVc), C02 transfer is limited to 13-19 % by DM and
to 81-89 % by 9Vc during rest as well as during work load of 75 W.
SYNTHESIS OF CARBON-14 LABELED ~-KETO ESTER VIA MAGNESIUM ETHYL MALONATE
H. Lee, P. Woo, L. Santay, A. Travalent, H. Roark, T. Capiris, and C.C. Huan~
Chemistry Department Parke-Davis Pharmaceutical Research Division Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI 48105 USA
~-Keto esters are versatile common intermediates for the synthesis of many types of pharmaceuticals. However, currently available methods of incorporating a radiolabel into a ~-keto ester oftentimes do not give reproducible and satisfactory results. A facile method using magnesium ethyl malonate based on modifications of the work of Bram and Vilkas (Bull. Soc. Chim., 945 (1964)) was developed for the synthesis of labeled ~-keto esters. For example, heating of magnesium ethyl malonate with labeled 1-[ C]acetylimidazole followed by acid hydT~lysis/decarboxylation gave a quantitative yield of ethyl [3-~C]acetoacetate. The method has also been applied to the synthesis of other labeled and unlabeled ~-keto esters with excellent results.
O
H ~ N ~.~0 ,''Mg ~ R CH2COOEt
0 0
OEt
