US EPA

8687064 

Journal Article 

Synthesis of dl-Sirenin and dl-Isosirenin 

Bhalerao, UT; Plattner, JJ; Rapoport, H 

1970 

Yes 

Journal of the American Chemical Society
ISSN: 0002-7863
EISSN: 1520-5126 

92 

11 

3429-3433 

English 

10.1021/ja00714a034 

A synthetic route to dl-sirenin and dl-isosirenin was achieved using the following sequence. 5-Bromovaleric acid on treatment with triphenylphosphine gave the phosphonium salt; Wittig reaction using this salt and 6- methyl-5-hepten-2-one gave the C13-diene acid, 6,10-dimethyl-5,9-undecadienoic acid, as a mixture of cis and trans isomers. Conversion to acid chloride and treatment with diazomethane gave the diazo ketone which, in refluxing cyclohexane in the presence of cupric sulfate, afforded both the endo- and exo-methyl isomers of 7-methyl-7-(4- methyl-3-pentenyl)bicyclo[4.1.0]heptan-2-one. Small amounts (ca. 1%) of the corresponding ten-membered ring systems were also isolated. Condensation of the bicyclic ketone with dimethyl carbonate gave a quantitative yield of β-keto ester which was reduced to an isomeric mixture of β-hydroxy esters by sodium borohydride. These β-hydroxy esters were dehydrated via the xanthate procedure or better by a base-catalyzed elimination of the pivaloyl derivatives to give a quantitative yield of the desiredα,β -unsaturated ester. Reduction of the esters with LiAlH4 gave monodeoxysirenin and monodeoxyisosirenin. Monodeoxysirenin also was obtained by treatment of natural l-sirenin with p-toluenesulfonyl chloride in pyridine, followed by reduction with LiAlH4. Oxidation of the unsaturated esters with selenium dioxide in ethanol gave in high yield and stereospecifically the trans-aldehydes. Finally, reduction of the aldehydes with LiAlH4-AlCl3 gave dl-sirenin and dl-isosirenin. dl-Sirenin was identical spectrally and chromatographically with natural l-sirenin. Bioassays on dl-sirenin, dl-isosirenin, and the monodeoxy derivatives are also reported. 1970, American Chemical Society. All rights reserved.