ChemInform Abstract: Regiochemical and Stereochemical Studies on Halogen-Induced Ring Expansions of Unsaturated Episulfides (original) (raw)
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2013
Synthesis and preliminary biological evaluation of a 35-member library of bistramide A stereoisomers are reported. All eight stereoisomers of the C1-C13 tetrahydropyran fragment of the molecule were prepared utilizing crotylsilane reagents 9 and 10 in our [4+2]-annulation methodology. In addition, the four isomers of the C14-C18 γ-amino acid unit were accessed via a Lewis acid mediated crotylation reaction with use of both enantiomers of organosilane 11. The spiroketal subunit of bistramide A was modified at the C39-alcohol to give another point of stereochemical diversification. The fragments were coupled by using a standard peptide coupling protocol to provide 35 stereoisomers of the natural product. These stereochemical analogues were screened for their effects on cellular actin and cytotoxicity against cancer cell lines (UO-31 renal and SF-295 CNS). The results of these assays identified one analogue, 1.21, with enhanced potency relative to the natural product, bistramide A.
The Journal of Organic Chemistry, 1987
Reaction of (trimethylsily1)methanesulfonyl chloride (6a) or-sulfonic anhydride (6b) with cesium fluoride in the presence of cyclopentadiene affords 2-thiabicyclo[ 2.2.lIhept-5-ene 2,a-dioxide (4) by way of sulfene CH2=S02. Similar reaction of (trimethylsily1)methanesulfinyl chloride (7) gave the unstable 2-thiabicyclo[2.2.1] hept-5-ene endo-2-oxide (3) via the intermediacy of sulfine CH2=S0. Compound 3 can be oxidized to 4 and reduced to 2-thiabicyclo[2.2.1]hept-5-ene (1) and the latter oxidized to the stable 2-thiabicyclo[2.2.1]hept-5-ene exo-2-oxide (2). Fluorodesilylation of 1-(trimethylsily1)propanesulfonic anhydride (8) in the presence of cyclopentadiene gave a 77/23 ratio of endo/exo-3-ethyl-2-thiabicyclo[2.2.l]hept-5-ene 2,2-dioxide (9a/b) by way of propanethial S,S-dioxide. The structure of the major isomer 9a was established by an X-ray structure of the corresponding exo-epoxide lla, formed from 9a by oxidation. Reaction of 4 with n-butyllithium followed by ethyl iodide gave a compound identical with minor isomer 9b. Reaction of propanethial S-oxide with cyclopentadiene gave unstable endo-3-ethyl-2-thiabicyclo[2.2.l]hept-5-ene endo-5-oxide (loa). The structure of loa was established by oxidation to sulfone 9a, by reduction and reoxidation to a stable exo-5-oxide lob, by its facile [2,3] sigmatropic rearrangement to exo-4-ethyl-2-oxa-3-thiabicyclo[3.3.0]oct-7-ene (14c), and by NMR spectroscopic methods. Compound 14c was characterized by NMR spectroscopy and by ita reactions. Oxidation of 14c gave the endolexo-3-oxides 15c/15c' and the 3,3-dioxide 16c. Reaction of 14c with phenyllithium gave alcohol 17c, which was desulfurized and oxidized to 5-propyl-2-cyclopentenone or was oxidized at both carbon and sulfur to give (E)-5-propylidene-2-cyclopentenone 21c on gentle warming. Reaction of 14c with tert-butyl alcohol gave exo-6-tert-butoxy-exo-3-ethyl-syn-7hydroxy-2-thiabicyclo[2.2.l]heptane (24), characterized by further oxidation to crystalline hydroxy sulfone 25 and keto sulfone 26. Mechanisms are proposed for the above series of reactions. (1) (a) The Chemistry of Sulfines. 13. (b) Part 12 Block, E.; Ahmad, S.
Journal of the American Chemical Society, 1986
J . Am. Chem. SOC. difficulty was overcome by using an excess of reagents and running the reaction under strict control. To a solution of ketone l a in benzene was added an excess of BF3.0Et2 (ca. 10 equiv to the substrate). The resulting dark violet solution was stirred for 30 min under a nitrogen atmosphere, and a large excess of diazomethane in ether, free from alcohols and moisture, was added to the solution of the aged complex. Chromatographic separation of the product yielded bridge-enlarged a-oxoferrocenophane 2a (1 8%) as orange-yellow crystals: mp >300 OC; IR, 1655 cm-I ( u~=~) ; high-resolution MS, m / z 470.2293 (calcd mol wt, 470.2270); I3C NMR (100.4 MHz, CDCI,) 6 24.2-44.3 (1 1 peaks, methylene C), 80.5-85.7 (six peaks, Cp C), 209.31 ( ' 2 4 ) ; absorption spectrum A, , , (THF), 425 nm (e 313). Reduction of the ketone 2a with LiAIH4/AICI3 in ether quantitatively gave the target compound 2a, as yellow needles: mp >300 "C; high-resolution MS, m l z 456.2470 (calcd mol wt, 456.2477); absorption spectrum A, , , (THF), 403 nm ( 6 89). The ' H N M R spectrum (400 MHz, CDCI,) of 2b showed two signals for the methylene resonances (6 1.97, wh/2 = 24.8 Hz, a-CH,; 6 2.54, Whp = 15.2 Hz, P-CH2).I9 No other signal was present. The 13C(1HJ NMR spectrum (25.1 MHz, CDC13), obtained under complete decoupling conditions, was dramatically simple as expected. Only three signals were observed at 6 84.46, 26.90, and 23.55, and these were assigned to the Cp rings and the pand a-methylene carbons,
Cycloadditions and Cyclizations of Acetylenic, Allenic, and Conjugated Dienyl Sulfones
Chemical Reviews, 2010
Cyclizations of Unsaturated Sulfones on Solid Supports 4546 19. Concluding Remarks 4547 20. Acknowledgments 4548 21. Note Added in Proof 4548 22. References 4548 2. Diels-Alder Cycloadditions 2.1. Unsaturated Sulfones as Dienophiles 2.1.1. Early Studies Numerous Diels-Alder reactions have been reported that successfully exploit the activating effect of the sulfone group Tom Back was born in Prague, Czechoslovakia, and grew up in Montreal, Canada, where he attended McGill University for both his undergraduate and graduate degrees. He obtained his Ph.D. in 1974 with Professor David N. Harpp and then spent two postdoctoral years at Imperial College in London, England, with Professor Sir Derek H. R. Barton. Upon his return to Canada in 1976, he joined the Division of Biological Sciences at the National Research Council of Canada in Ottawa, where he worked in the laboratory of Dr. O. E. Edwards. In 1978 he moved to the University of Calgary and was promoted to Full Professor in 1987. Apart from a sabbatical leave with Professor Carl Djerassi at Stanford University in 1985, he has remained at the University of Calgary. He was elected a Fellow of the Chemical Institute of Canada in 1990, was the 2006 recipient of the Faculty of Science Research Excellence Award, and in 2008 received the Alfred Bader Award from the Canadian Society for Chemistry. When not on campus, he enjoys mountaineering and ice climbing in the Canadian Rockies. Kristen Clary was born in Kamloops, BC, Canada, in 1984. She obtained her B.Sc. Degree from the University of Calgary in 2006. She is currently a Ph.D. candidate under the direction of Professor Tom Back. Her research focuses on the vinylogous aza-Morita-Baylis-Hillman reaction and its application to the total synthesis of natural products.
The synthesis and reactions of 4-carbomethoxy β-sultams
Tetrahedron Letters, 1989
The preparation of 4carbomefhauy-I ,2-thiazetidine-l, l-dimides from carbometw-methanesu2fonyl chioti and imines is described. The ability of p-lactam antibiotics to acylate bacterial cell wall enzymes provides the biochemical basis for their bactericidal action. Although structural analogs of p-la&am antibiotics have been intensively investigated for more than forty years. until quite recently scant attention has been focused on replacement of the azetidinone ring by more reactive entities. 1 The 1.2~thiazetidine