Academic literature on the topic 'Fukuyama-Mitsunobu reaction'

Thesis titled, “Design, Synthesis and Conformational Analysis of Hydrogen Bond Surrogate (HBS) Stabilized Helices in Natural Sequences. Helically Constrained Peptides for Potential DNA-Binding”, describes the development of a novel covalent hydrogen bond surrogate (HBS) model and its incorporation in short (4-8 residues) unstructured peptide sequences with coded amino acids, through a facile solution phase synthetic method (SPSM), to constrain them into α- helical conformations with highest known stabilities and helicities. The synthetic protocol was developed for mass scale combinatorial synthesis of helical peptidomimetics. NMR, FT-IR, CD spectra and molecular dynamics simulations of variants of the HBS-constrained helical peptidomimetics were analyzed to determine the optimum number of sp2 atoms and the residue preferences that yield both the α-helical and the 310-helical folds with high structural integrity in the shortest sequences. The HBS-constrained helical peptidomimetics were used to derive experimental evidence that the 2-state Helix-Coil Transition occurs at each residue during helix folding and that this process is entropically driven. Further, the role of temperature on the denaturation of secondary structures was investigated using these HBS-constrained helical models. Helical peptidomimetics of the DNA-binding domain in the zinc-finger human TTK protein have been synthesized, which have proven to be promising mimics for DNA-binding and subsequent transcription regulation.
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V. T. Perchyonok and Kellie L. Tuck of Monash University found (Tetrahedron Lett. 2008, 49, 4777) that a concentrated solution of Bu4NCl and H3PO2 in water effected free radical reductions and cyclizations. Stéphane G. Ouellet of Merck Frosst demonstrated (Tetrahedron Lett. 2008, 49, 6707) that an oxazoline such as 3 could be converted to the alcohol 4 by acylation followed by reduction. Elizabeth R. Burkhardt of BASF developed (Tetrahedron Lett. 2008, 49, 5152) a protocol for scalable reductive amination using an easily metered liquid pyridine-borane complex. Mohammad Movassaghi of MIT devised (Angew. Chem. Int. Ed. 2008, 47, 8909) a strategy for conversion of an allylic carbonate 8 by way of the allylic diazene to the terminal alkene 9. Philippe Compain of the Université d’Orleans uncovered (J. Org. Chem. 2008, 73, 8647) a practical procedure for oxidizing an inexpensive aldose such as 10 to the amide 12, a valuable chiral pool starting material. Karl A. Scheidt of Northwestern University extended (Organic Lett. 2008, 10, 4331) activated MnO2 oxidation to saturated aldehydes such as 13, leading to the ester 15. Tohru Fukuyama of the University of Tokyo showed (Organic Lett. 2008, 10, 2259) that halides such as 16 could be oxidized to the oxime 18 with the reagent 17. The product oximes are readily dehydrated to the corresponding nitriles. Chutima Kuhakarn of Mahidol University devised (Synthesis 2008, 2045) a simple protocol for the oxidation of a primary amine such as 19 to the nitrile 20 . Nasser Iranpoor and Habib Firouzabadi of Shiraz University developed (J. Org. Chem. 2008, 73, 4882) the reagent 22 for Mitsunobu coupling. The stereochemical course of this reaction with simple acyclic secondary alcohols such as 21 was not reported. Salvatore D. Lepore of Florida Atlantic University optimized (Angew. Chem. Int. Ed. 2008, 47, 7511) the quisylate 24 for the displacement with retention to give the azide 25. Hideki Yorimitsu and Koichiro Oshima of Kyoto University optimized (J. Am. Chem. Soc. 2008, 130, 11276) a Co catalyst for the conversion of a secondary halide such as 26 to the terminal alkene 27 . Base-mediated elimination gave primarily the internal alkene.

The denudatine alkaloids, exemplified by (−)-lepenine 3, have been converted chem­ically into the physiologically-active aconitine alkaloids. Tohru Fukuyama of Nagoya University envisioned (J. Am. Chem. Soc. 2014, 136, 6598) an intramolecular Mannich condensation, the conversion of 1 to 2, that in a single step would assemble two of the six rings of 3. The starting material for the synthesis was the ether 4, prepared by Mitsunobu cou­pling of the phenol with L-lactic acid methyl ester. Reduction of the ester to the alde­hyde followed by the addition of vinylmagnesium chloride led to the secondary allylic alcohol. Claisen rearrangement with triethyl orthoacetate delivered not the ether, but rather 5, the desired product of an additional Claisen rearrangement. The phenol of 5 was protected as the mesylate, that was then subjected to ozonolysis with a reduc­tive workup to give the primary alcohol. This was protected as the pivalate, which was selectively saponified. The resulting carboxylic acid was cyclized to 6 using trifluoro­acetic anhydride. The triene 7 was prepared from 6 by the addition of vinylmagnesium chloride fol­lowed by dehydration. Prospective intramolecular Diels–Alder cycloadditions that would form five-or six-membered ring lactones often fail. In the event, the cycliza­tion of 7 to the seven-membered ring lactone 8 proceeded smoothly. The tetracyclic 8 could be brought to high ee by recrystallization. Hydroboration followed by reduc­tion then delivered the diol aldehyde 9, that was converted to 1 by reductive amina­tion followed by protection and oxidation. On deprotection, 1 cyclized to the iminium salt 10. Intramolecular Mannich addi­tion of the enol form of the ketone then proceeded, to give 2. It is possible to protect tertiary amines, inter alia by formation of the adduct with a borane. In this case, transient protection as the hydrochloride was sufficient to allow oxidation of the alcohol derived from 2 to the diene 11. This was reactive enough to undergo the Diels–Alder addition of ethylene, from the more open face, leading to 12. The now-extraneous methoxy groups were then removed reductively to give 13, and the last stereogenic center of 3 was installed by hydroboration of the alkene. Methylenation of 14 followed by Luche reduction then completed the synthesis of (−)-lepenine 3.