First Synthesis of (20S) 3β,16β-Dihydroxy-5-pregnen-20,16-carbolactone (Diosgeninlactone)

Abstract

first_page settings Order Article Reprints Font Type: Arial Georgia Verdana Font Size: Aa Aa Aa Line Spacing:    Column Width:    Background: Open AccessAbstract First Synthesis of (20S) 3β,16β-Dihydroxy-5-pregnen-20,16-carbolactone (Diosgeninlactone) by Andrea C. Bruttomesso and Eduardo G. Gros * Departamento. de Química. Orgánica, UMYMFOR. Facultad de Ciencias Exactas y Naturales, UBA. Pabellón II, 3º P. Ciudad Universitaria. (1428). Buenos Aires, Argentina * Author to whom correspondence should be addressed. Molecules 2000, 5(3), 564-565; https://doi.org/10.3390/50300564 Published: 22 March 2000 Download Download PDF Download PDF with Cover Download XML Versions Notes Abstract: Diosgeninlactone (1), a natural product from Solanum vespertilio, was stereoselectively synthesized in high yield from 3β-hydroxy-5-androstene. IntroductionOur development of synthetic approaches to cis-20,16-γ-carbolactones originated during the course of studies on the catabolic pathway by which tomato plants degrade steroidal alkaloids into 3β-hydroxy-5α-pregn-16-en-20-ona.The isolation of some related compounds, such as (23R)-23-acetoxytomatidine and (23S)-23-acetoxysoladulcidine from Lycopersicum esculentum, suggested a probable mechanism for the degradation of nitrogen containing rings [1].In addition, products containing the 20,16-cis-γ-lactone moiety have been isolated from different vegetable sources, and postulated to be metabolic products of the corresponding sapogenins. At the moment none of them have been synthesized. In 1971 Diosgeninlactone (1) was isolated from the ethanolic extract of the fruits of Solanum vespertilio [2].In view of the highly efficient protocol developed by us, in the synthesis of tigogeninlactone [3,4] we decided to explore this synthetic strategy to obtain 1. ExperimentalWittig reaction on 3β-(dimethyl-t-butylsilyloxy)-5-androsten-17-one yielded the Z-olefin stereoselectively with the introduction of a two-carbon lateral side chain at C-17.Allylic hydroxylation on C-16 with t-butylhydroperoxide in the presence of catalytic amounts of selenium dioxide introduced the hydroxy group from the α-face of the steroid nucleus.Swern oxidation produced the conjugated ketone 3 in very good yield.Michael addition of sodium cyanide in a THF/EtOH/H2O mixture introduced the third carbon atom in the side chain. The addition from the α-face afforded only the 17β-(20S) nitrile isomer.Stereoselective reduction of the ketonitrile with lithium tri-t-butoxy aluminohydride produced the 16β-hydroxy-derivative. As expected, the bulky hydride approaches the carbonyl group from the lesshindered α-face, producing in excellent yield and selectivity the needed β-orientation for the hydroxy group on C-16.Alkaline hydrolysis of the hydroxy-nitrile followed by an acidic work-up produced lactone 1, as lactonization and deprotection of the 3β-OTBDMS group took place during acidic work-up. Results and ConclusionsMany strategies have been explored for the construction of the β-fused γ-lactonic ring E. The attachment of a 2-carbon side chain on C-17 previously to the allylic oxidation of C-16 was the key step in the synthesis.Early studies involving the connection of a 3-carbon side chain on C-17 of a 17-oxo-16β-acetoxyandrostane led to the epimeric α-oriented γ-lactone [3,4].In conclusion, a highly efficient stereoselective protocol has been developed for the β-oriented 20,16-cis-γ-carbolactones. Thus, Diosgeninlactone (1) were stereoselectively synthesized in high yield from 3β-hydroxy-5-androsten-17-one (2). AcknowledgmentsWe thank Universidad de Buenos Aires and CONICET (Argentina) for partial financial support.References and NotesNagaoka, T.; Yoshihara, T.; Ohra, J.; Sakamurja, S. Phytochemistry 1993, 34, 1153. González, A. G.; Fransisco, C. G.; Barreira, R. F.; Lopez, E. S. An. Quím. 1971, 67, 433, (Chem. Abst. 1971, 75, 115890n). Bruttomesso, A.; Doller, D.; Gros, E. G. Synth. Comm. 1998, 28, 4043. Bruttomesso, A.; Doller, D.; Gros, E. G. Bioorg. Med. Chem. 1999, 7, 943. [PubMed] Share and Cite MDPI and ACS Style Bruttomesso, A.C.; Gros, E.G. First Synthesis of (20S) 3β,16β-Dihydroxy-5-pregnen-20,16-carbolactone (Diosgeninlactone). Molecules 2000, 5, 564-565. https://doi.org/10.3390/50300564 AMA Style Bruttomesso AC, Gros EG. First Synthesis of (20S) 3β,16β-Dihydroxy-5-pregnen-20,16-carbolactone (Diosgeninlactone). Molecules. 2000; 5(3):564-565. https://doi.org/10.3390/50300564 Chicago/Turabian Style Bruttomesso, Andrea C., and Eduardo G. Gros. 2000. "First Synthesis of (20S) 3β,16β-Dihydroxy-5-pregnen-20,16-carbolactone (Diosgeninlactone)" Molecules 5, no. 3: 564-565. https://doi.org/10.3390/50300564 Find Other Styles Article Metrics No No Article Access Statistics For more information on the journal statistics, click here. Multiple requests from the same IP address are counted as one view.