- Synthesis of a Chloroalkene Dipeptide Isostere-Containing Peptidomimetic and Its Biological Application
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The first rapid and efficient chemical synthesis of a cyclic Arg-Gly-Asp (RGD) peptide containing a chloroalkene dipeptide isostere (CADI) is reported. By a developed synthetic method, an N-tert-butylsulfonyl protected CADI was obtained utilizing diastereoselective allylic alkylation as a key reaction. This CADI was also transformed into an N-Fmoc protected CADI in a few steps. The CADI was used in Fmoc-based solid-phase peptide synthesis. The first synthesis of a CADI-containing cyclic RGD peptide was successful, and the synthesized CADI-containing peptidomimetic was found to be a more potent inhibitor against integrin-mediated cell attachment than the parent cyclic peptide.
- Kobayakawa, Takuya,Matsuzaki, Yudai,Hozumi, Kentaro,Nomura, Wataru,Nomizu, Motoyoshi,Tamamura, Hirokazu
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supporting information
p. 7 - 11
(2018/05/04)
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- Asymmetric vinylogous Mannich reactions: A versatile approach to functionalized heterocycles
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Asymmetric vinylogous Mannich reaction (VMR) of 2-(tert- butyldimethylsilyloxy)furan (TBSOF, 1) with (RS)- or (S S)-t-BS-imines (3) furnished 5-aminoalkylbutenolides 7a-k in 75-87% yields with anti/syn ratios ranging from 75:25 to 97:3. Butenolides 7a-f,k were readily converted into substituted lactones 8 and 5 and 6-substituted 5-hydroxypiperidin-2-ones 11a-g, which are, in turn, key intermediates for the synthesis of many bioactive compounds.
- Ruan, Shu-Tang,Luo, Jie-Min,Du, Yu,Huang, Pei-Qiang
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supporting information; experimental part
p. 4938 - 4941
(2011/11/06)
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- Further studies toward the stereocontrolled synthesis of silicon-containing peptide mimics
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Further studies are reported on the utilization of the versatile reaction between chiral sulfinimines and alkyldiphenylsilyl lithium reagents with the goal of preparing a wide range of silanediol-based protease inhibitors. In particular, focus has been placed to demonstrate how a number of genetically encoded amino acid side chains such as serine, threonine, tyrosine, lysine, proline, arginine, aspartate and asparagine might be incorporated into the overall approach. Efforts to apply this synthetic methodology for accessing biologically relevant silanediol dipeptide mimics are also described. This includes the synthesis of a potential inhibitor of the human neutrophil elastase, as well as a diphenylsilane mimic of a hexapeptide fragment of the human islet amyloid polypeptide.
- Hernandez, Dacil,Lindsay, Karl B.,Nielsen, Lone,Mittag, Tina,Bjerglund, Klaus,Friis, Stig,Mose, Rasmus,Skrydstrup, Troels
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supporting information; experimental part
p. 3283 - 3293
(2010/08/07)
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- Stereocontrolled synthesis of methyl silanediol peptide mimics
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(Chemical Equation Presented) The treatment of chiral sulfinimines with (methyldiphenylsilyl)lithium gives α-(methyldiphenylsilyl)-sulfinamides with excellent diastereoselectivity, and in good yield. The presence of α-protons on the imines is also well tolerated. The sulfanamide auxiliary is easily removed via treatment with methanolic HC1 and the resulting amine extended into peptide chains accordingly. The diphenylsilyl moiety is a resilient protecting group for the corresponding silanediol, which can be unmasked via treatment with TfOH, followed by aqueous hydrolysis. The crude silanediol may be isolated and purified as its corresponding bis-TMS siloxane via protection with TMSC1, and converted back to the desired silanediol via hydrolysis with aqueous KOH. Efforts to apply this approach to biologically relevant silanediol peptide mimics, with a view to protease inhibition, are described.
- Nielsen, Lone,Lindsay, Karl B.,Faber, Jesper,Nielsen, Niels Christian,Skrydstrup, Troels
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p. 10035 - 10044
(2008/04/05)
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- Highly diastereoselective reactions of 2-lithiated indoles with chiral N-tert-butanesulfinyl aldimines for the synthesis of chiral (2-indolyl) methanamine derivatives
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Nucleophilic addition reactions of 2-lithiated N-phenylsulfonylindoles with (R)-N-tert-butanesulfinyl aldimines provided chiral (2-indolyl) methanamine derivatives in moderate to good yields (up to 100%) with excellent diastereoselectivities (>99:1), in which no additional Lewis acids were required.
- Cheng, Liang,Liu, Li,Sui, Yong,Wang, Dong,Chen, Yong-Jun
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p. 1833 - 1843
(2008/02/12)
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- The total synthesis of tubulysin D
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The first total synthesis of tubulysin D is reported. The development and application of new tert-butanesulfinamide methods allowed for rapid syntheses of the tubuvaline and tubuphenylalanine fragments. Most significantly, a route was devised and implemen
- Peltier, Hillary M.,McMahon, Jeffrey P.,Patterson, Andrew W.,Ellman, Jonathan A.
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p. 16018 - 16019
(2007/10/03)
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- Synthesis of enantiomerically pure N-tert-butanesulfinyl imines (tert- butanesulfinimines) by the direct condensation of tert-butanesulfinamide with aldehydes and ketones
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Experimental details for the first general methods for the one-step preparation of N-tert-butanesulfinyl imines (tert-butanesulfinimines) (2) from aldehydes and ketones is described. To effect the condensations of tert- butanesulfinamide (1) with aldehydes, the Lewis acidic dehydrating agents MgSO4, CuSO4, or Ti(OEt)4 are employed. Aldehyde condensations mediated by MgSO4 proceed in high yields (84-96%) when an excess of aldehyde is used. In contrast, only a slight excess of aldehyde (1.1 equiv) relative to tert- butanesulfinamide provides sulfinimines in high yields when the more Lewis acidic dehydrating agent CuSO4 is used. The CuSO4-mediated procedure is effective for a wide range of aldehydes, including sterically demanding aldehydes, such as isobutyraldehyde (90%), and electron-rich aldehydes, such as p-anisaldehyde (81%). The still more Lewis acidic Ti(OEt)4 and TI(O-i- Pr)4 also afford N-tert-butanesulfinyl aldimines from especially unreactive aldehydes, such as pivaldehyde (82%). In addition, Ti(OEt)4 is effective for the condensation of 1 with ketones to afford a wide range of N-tert- butanesulfinyl ketimines in good yields (77-91%). For sulfinyl ketimines derived from methyl or n-alkyl phenyl ketones and methyl or n-alkyl isopropyl ketones, only the E isomer is detected by 1H and 13C NMR in CDCl3. For those cases where the difference in steric demand about the imine is very small, such as for 2-hexanone, high E/Z ratios are still observed (5:1).
- Liu,Cogan,Owens,Tang,Ellman
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p. 1278 - 1284
(2007/10/03)
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