23) Literature rotation data for (-)-swainsonine is variable ranging from -67.4°(c 0.33, MeOH)5a to -87.2°(c 2.1, MeOH).lb Because of the nature of our synthesis, we do not believe that our rotation data is indicative of diminished enantiomeric purity.(24) We thank Professor H. F. Lodish and N. H. Kong of the M.I.T. Biology Department for performing this biological assay.(25) Note Added in Proof: We have recently completed the syntheses of these two ("gluco" and "galacto") swainsonine isomers.
A diastereoselective synthesis of the tetrahydropyranochromene ring system common to several natural product isolates of Alpinia blepharocalyx is reported. We have shown that a stereochemical preference exists for a syn configuration between the anomeric aryl substituents, representative of the C-7 and C-7′ substituents in the natural products. Further, our results show that stereocontrol is under kinetic control, and calculations suggest that a favorable π-stacking interaction may be the source of this stereocontrol.More than fifty polyphenolic constituents of the seeds of Alpinia blepharocalyx have been isolated by Kadota and coworkers, 1 and several of them have been shown to possess significant antiproliferative activity against colon 26-L5 carcinoma and HT-1080 fibrosarcoma cells. Not surprisingly, these compounds have attracted the attention of several groups, resulting in both partial 2 and total 3 syntheses of a number of analogues. Calyxin I (1) along with the epimeric analogues calyxin J (2) and epicalyxin J (3) comprise a subset of isolates that are characterized by the presence of a novel bis-C-arylpyranoside moiety embedded in a tetrahydropyranochromene framework. To date, synthetic work in this area has been sparse. Li and coworkers have reported stereoselective syntheses of compounds 4 and 5 using the Prins cyclization, 4 but they did not report the formation of bis-aryl derivatives by their route. We therefore chose compound 6 as a model synthetic target to see if a stereochemical preference exists for the aryl substituents to be syn to each other as indicated, analogous to the C-7 and C-7′ positions in the natural products. The nature of the interaction between the two aromatic rings at these positions would be important, and the possibility of a favorable π-stacking effect was not ruled out as a controlling factor. 5 kmead@ra.msstate.edu. Supporting Information Available: 1 H and 13 C spectra for new compounds, and details of the computational studies. This material is available free of charge via the Internet at http://pubs.acs.org. Our route began with the racemic lactone 8, which was prepared in 56% yield by a palladiumcatalyzed addition of 2-benzyloxy-iodobenzene 7 6 to 5,6-dihydro-2H-pyran-2-one (Scheme 1). A directed aldol reaction of lactone 8 with p-methoxybenzaldehyde, via its boron enolate, then gave alcohol 9 in a 91% yield as a single isomer, 7 which was cleanly converted to the diol 10 in 94% yield under standard hydrogenation conditions. Exposure of diol 10 to Lewis acid then provided compound 11 diastereomerically pure (79% from compound 9). The stereochemistry of compound 11 was easily assignable based on proton NMR coupling constants. A doublet at δ5.22 (J = 10 Hz) established the trans-diaxial relationship between H a and H b , while a doublet of doublets at δ3.08 (J = 10, 13 Hz) confirmed the same relationship between H a and H c . Although the formation of 11 from diol 10 proceeded with complete inversion of configuration, establishment of the newly-formed ring stere...
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