- Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin i
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A 14-step biomimetic synthetic route to glyceollin I (1.5% overall yield) was developed and deployed to produce the natural enantiomeric form in soy, its unnatural stereoisomer, and a racemic mixture. Enantiomeric excess was assessed by asymmetric NMR shift reagents and chiral HPLC. Antiproliferative effects were measured in human breast, ovarian, and prostate cancer cell lines, with all three chiral forms exhibiting growth inhibition (GI) in the low to mid μM range for all cells. The natural enantiomer, and in some cases the racemate, gave significantly greater GI than the unnatural stereoisomer for estrogen receptor positive (ER+) versus ER- breast/ovarian cell lines as well as for androgen receptor positive (AR+) versus AR - prostate cancer cells. Surprisingly, differences between ER + and ER- cell lines were not altered by media estrogen conditions. These results suggest the antiproliferative mechanism of glyceollin I stereoisomers may be more complicated than strictly ER interactions.
- Khupse, Rahul S.,Sarver, Jeffrey G.,Trendel, Jill A.,Bearss, Nicole R.,Reese, Michael D.,Wiese, Thomas E.,Boue, Stephen M.,Burow, Matthew E.,Cleveland, Thomas E.,Bhatnagar, Deepak,Erhardt, Paul W.
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experimental part
p. 3506 - 3523
(2011/07/30)
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- Multigram synthesis of glyceollin i
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Scaled-up procedures and preparation of glyceollin I in multigram quantities are described. The synthesis features construction of a cis-fused ring system in high enantiomeric excess after Sharpless asymmetric dihydroxylation of a key intermediate that is initially produced by an intramolecular Wittig reaction to afford the requisite alkene while simultaneously forming the first ring. The overall yield is 12% after 11 steps.
- Luniwal, Amarjit,Malik, Neha,Erhardt, Paul,Khupse, Rahul,Reese, Michael,Liu, Jidong,El-Dakdouki, Mohammad,Fang, Lei
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p. 1149 - 1162
(2012/01/05)
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- METHODS FOR SYNTHESIZING GLYCINOLS, GLYCEOLLINS I AND II, COMPOSITIONS OF SELECTED INTERMEDIATES, AND THERAPEUTIC USES THEREOF
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Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, dietary supplements and ethical pharmaceutical agents.
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Page/Page column 2; 5; 14
(2011/06/26)
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- Total syntheses of racemic, natural (-) and unnatural (+) glyceollin I
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(Chemical Equation Presented) The first total syntheses of racemic glyceollin I and its enantiomers are described. A Wittig approach was utilized as an entry to the appropriately substituted isoflav-3-ene so that an osmium tetroxide mediated asymmetric dihydroxylation could be deployed for stereospecific Introduction of the 6a-hydroxy group. While using triphenylphosphine hydrobromide, a novel method was found for gently removing MOM from protected phenolic hydroxyl groups present within sensitive systems.
- Khupse, Rahul S.,Erhardt, Paul W.
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supporting information; experimental part
p. 5007 - 5010
(2009/05/31)
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