Carpaine
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| Names | |
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| IUPAC name
(1S,11R,13S,14S,24R,26S)-13,26-Dimethyl-2,15-dioxa-
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| Other names
(+)-Carpaine
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| Identifiers | |
3D model (JSmol)
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| ChEBI | |
| ChemSpider | |
| ECHA InfoCard | 100.020.378 |
PubChem CID
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| Properties | |
| C28H50N2O4 | |
| Molar mass | 478.70 g/mol |
| Melting point | 121 °C |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Carpaine is one of the major alkaloid components of papaya leaves which has been studied for its cardiovascular effects.[2] Circulatory effects of carpaine were studied in Wistar male rats weighing 314 +/- 13 g, under pentobarbital (30 mg/kg) anesthesia.[3] Increasing dosages of carpaine from 0.5 mg/kg to 2.0 mg/kg resulted in progressive decrease in systolic, diastolic, and mean arterial blood pressure. Selective autonomic nervous blockade with atropine sulfate (1 mg/kg) or propranolol hydrochloride (8 mg/kg) did not alter the circulatory response to carpaine. Carpaine, 2 mg/kg, reduced cardiac output, stroke volume, stroke work, and cardiac power, but the calculated total peripheral resistance remained unchanged. It is concluded from these results that carpaine affects the myocardium directly. The effects of carpaine may be related to its macrocyclic dilactone structure, a possible cation chelating structure.
Structures History
After the first isolation of Carpaine by Greshoff in 1890, Merck & Company assigned the empirical formula C14H27NO2 to it, which was soon corrected to C14H25NO2 by van Rijn.[4] In 1930s, Barger and his collogues investigated various degradation products of Carpaine and was able to obtain a series of chemical structures of Carpaine.[5]
Then in 1953, Rapoport and his collogues at the University of California obtained a new form of Carpaine chemical structure which they found the nitrogen-containing ring had a piperidine structure instead of the pyrrolidine as previously thought; they also located the position of the lactone ring between atoms numbered 3 and 6 on the piperidine nucleus.[4] Later work from Govindachari & Narasimhan and Tichy and Sicher further confirmed the structural formula for Carpaine.[4]
However, Spiteller-Friedmann and Spiteller used mass spectrometry to discover that the molecular weight of Carpaine is closer to 478, which is represented by twice of the original empirical formula.[6] The new finding proved that Carpaine consists of two identical halves, which form a 26-membered cyclic diester, or dilactone, with an empirical formula of C28H50N2O4, and the configuration was finally determined by Coke and Rice in 1965.[4]
Isolation of Carpaine
The characterization of the powdered Carica papaya leaves, which the main active constituent is the macrocyclic lactone carpaine. Carpaine occurs in papaya leaves in concentrations as high as 0.4%, which is enough to make it available commercially at very reasonable costs.[4] In order to isolate carpaine by HPLC method, the plant leaves were first dried in an electric blast drying oven until constant mass, then the dried leaves were milled to fine powder. The powdered plant material were macerated with a mixed solution of ethanol/water/HCl for 24 hr at room temperature. The extract was then removed, stored, and desiccated, and this process was repeated five times. The whole extracts were pooled, and evaporated. The extract was then dissolved in water/HCl mixture, filtered, and extracted with petroleum ether to remove fat materials. The acid fraction was adjusted to pH 8.0 ~ 9.0 using [[NH4OH]] solution and extracted with chloroform. The chloroform fractions were pooled and evaporated. The whole operation was repeated again and the crude alkaloid carpaine was obtained.[7]
Mechanism of action
Pharmacology
References
- ^ Merck Index, 11th Edition, 1866.
- ^ Burdick, Everette M. "Carpaine. An alkaloid of Carica papaya. Chemistry and pharmacology." Economic Botany (1971), 25(4), 363-365.
- ^ Hornick, C. A.; Sanders, L. I.; Lin, Y. C. "Effect of carpaine, a papaya alkaloid, on the circulatory function in the rat." Research Communications in Chemical Pathology and Pharmacology (1978), 22(2), 277-289.
- ^ a b c d e Burdick, Everette. "Carpaine: An Alkaloid of Carica Papaya: Its Chemistry and Pharmacology". JSTOR.
- ^ Barger, G.; Robinson, Robert; Urushibara, Y. (1937). "141. Synthetical experiments relating to carpaine. Part I. Synthesis of a basic long-chain lactone". Journal of the Chemical Society (Resumed): 714. doi:10.1039/JR9370000714.
- ^ Friedrich‐Fiechtl, Jürgen; Spiteller, Gerhard (November 1971). "Anwendung der Massenspektrometrie zur Strukturaufklärung von Alkaloiden, X. Neue Alkaloide aus Erythrophleum guineense und über das Muawin". Chemische Berichte. 104 (11): 3535–3548. doi:10.1002/cber.19711041118.
- ^ "Isolation and Identification Carpaine in Carica papaya L. Leaf by HPLC-UV Method". International Journal of Food Properties.