The Synthesis of Delphinine: A Stereoselective Total Synthesis of an Optically Active Advanced Relay Compound

Wiesner, K.; Jay, Ernest; Tsai, T. Y. R.; Demerson, Christopher A.; Jay, Lizzie; Kanno, Toshio; Křepinský, Jiří J.; Vilim, A.; Wu, Changqi

doi:10.1139/v72-308

Cited by 16 publications

(7 citation statements)

References 7 publications

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“…The starting materials for the present synthesis were the compounds 7 and 16 both of which we have previously reported (4,5). However, both these compounds were now prepared by fundamentally improved methods.…”

Section: Discussionmentioning

confidence: 99%

“…tion of 1 3 with sodium hydride and benzyl chloride in dioxane, followed by the treatment of the product 1 4 with acetic acid at 45 "C for 24 h. The overall yield of the alcohol 1 5 from the starting material 10 was 5870. The conversion of 1 5 to the bromide 16 was performed as reported previously (5).…”

Section: Discussionmentioning

confidence: 99%

“…The attachment of the side chain to the aldehyde 9 was carried out as in the previously reported cases (3,5). Conlpound 9 was added t o an excess ofthe Grignard reagent prepared from the bromide 16 and the oily diastereoisomeric mixture 1 7 was isolated in a 90% yield.…”

Section: Discussionmentioning

confidence: 99%

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The synthesis of chasmanine: aromatic intermediate

Lee¹,

Sathe²,

Sy³

et al. 1976

Can. J. Chem.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The synthesis of chasmanine: aromatic intermediate

Lee¹,

Sathe²,

Sy³

et al. 1976

Can. J. Chem.

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“…Given the significant enantioselection found with some of our chiral selector resin beads, we tested their ability to resolve related proline derivatives lacking the dyes. The experiment was a kinetic resolution , that entailed stirring an excess of a chiral selector resin with a racemic proline pentafluorophenyl ester while monitoring the quantity and % ee of the proline derivative remaining in solution after filtering away the beads. Using MeO-Iso-Pro-OC 6 F 5 and the chiral selector resin DAsn-( RR )B-( RRRR )C in CHCl 3 , the kinetic resolution results shown in Figure A were obtained.…”

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confidence: 99%

Enantioselective Resolving Resins from a Combinatorial Library. Kinetic Resolution of Cyclic Amino Acid Derivatives

1998

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Solid materials that bind small molecules enantioselectively are valuable as resolving agents in chiral separations. Coupled with modern HPLC, even modestly enantioselective materials (e.g., with separation factors (R) as low as 1.1) are commonly used to resolve small organic compounds. 1,2 While such methods work well for analytical resolutions, large-scale chromatographic resolutions are often less practical. 3 If however a tightly binding and highly enantioselective (e.g., R g 10) resin or other solid material were readily available, then it would be possible to resolve compounds by simply stirring the racemate with such a resin and filtering. 4 The quest for highly enantioselective materials primarily for use in chiral chromatography is an active area of research.Typical methodologies involve structure-based design and empirical modification of known chiral selector molecules. 5 In this paper, we describe a new approach that involves the parallel synthesis and screening of a combinatorial library of potential chiral selectors on polystyrene synthesis beads. 6 Our screen allows picking the most enantioselective library member beads by visual inspection under a low-power microscope. We demonstrate the feasibility of this approach by making and screening a small (60member) combinatorial library of potential resolving resins and showing that enantioselective library members can be readily distinguished and used in a heterogeneous kinetic resolution process that corresponds to resolution by filtration.An Enantioselectivity Screen. To find the most enantioselective members of our chiral selector library, we developed a simple two-color differential binding screen that allows us to estimate the enantioselectivity of each library member visually. 6c,7 The screen employs enantiomeric probe molecules that are labeled with different colored dyes. In this work, we were seeking chiral selectors for resolving amino acid derivatives and suitable probes thus included the blue L-amino acid L-1 and the red D-amino acid D-1.The idea was to treat an equimolar mixture of these colored probe molecules with a library of chiral selectors on synthesis beads in which each bead carried a different selector. The result of such an experiment would be that highly enantioselective binding would yield beads that were red or blue whereas unselective binding would yield beads that were brown. 8The particular probes we used are shown above as 2 and 3. The commercially available Disperse Blue and Red dyes (bound to LPro and DPro derivatives respectively) we used were chosen to be visually distinct and not significantly bound by our selector library members. We also varied linkers (here succinyl and isophthaloyl) connecting the dye labels to the proline derivatives we wished to resolve.A Chiral Selector Library. For our library of chiral selectors, we prepared a library of chiral amines whose members could react with and bind to probes 2 or 3 either by acylation or salt formation, respectively. To promote significant enantioselectivity in the...

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“…1 To date, extensive synthetic efforts have resulted in the successful total syntheses of atisine, 2,3 veatchine, 3−5 garryine, 3,5 delphinine, 6 talatisamine, 7 napelline, 8 chasmanine, 9 nominine, 10 and neofinaconitine. 11 As shown in Figure 1, the denudatine family is a group of diterpenoid alkaloids containing more than 30 compounds, such as denudatine (1), 12,13 lepenine (2), 12,14 stenocarpine (3), 15 dictysine (4), 16 aconicarmine (5), 17 and kirinine B (6). 18 These compounds are especially interesting because they are chemical 9 and biosynthetic 19 precursors of aconitine-type alkaloids, which are well-known for their potent bioactivity such as inhibition of the voltage-dependent sodium ion channel.…”

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confidence: 99%