Peptide olefinic

An efficient method for the oxidative cleavage of solid-supported peptide olefins into aldehydes using a combination of OsOa/NalOa/DABCO system was described by Meldal and coworkers. The resulting aldehydes are subjected to intermolec-ular (V-acylium Pictet-Spengler reactions to furnish pyrroloiso-quinoline derivatives in high purity (eq 76). ... 

Two disadvantages are associated with the use of S-acetyl or 5-benzoyl derivatives in peptide syntheses (a) base-catalyzed hydrolysis of 5-acetyl- and 5-benzoylcys-teine occurs with /S-elimination to give olefinic side products, CH2=C-(NHPG)CO—(b) the yields of peptides formed by coupling an unprotected amino group in an 5-acylcysteine are low because of prior S-N acyl migration. ... 

Nucleophilic substitution reactions of halide anions in aprotic solvents are often accompanied by elimination reactions. For instance, reactions of secondary alkyl halides with potassium fluoride solubilized in acetonitrile with the aid of 18-crown-6 [3] give olefins as the main reaction product (Liotta and Harris, 1974). Similarly, the dicyclohexyl-18-crown-6 complex of potassium iodide acted exclusively as a base in its reaction with 2-bromo-octane in DMF (Sam and Simmons, 1974). The strongly basic character of weakly solvated fluoride has been exploited in peptide synthesis (Klausner and Chorev, 1977 Chorev and Klausner, 1976). It was shown that potassium fluoride solubilized... 

Krelaus R, Westermann B (2004) Preparation of peptide-like bicyclic lactams via a sequential Ugi reaction - olefin metathesis approach. Tetrahedron Lett 45 5987-5990... 

The other possibility is to coat the silica with a polymer of defined properties (molecular weight and distribntion) and olefin groups, e.g., polybutadiene, and cross-linked either by radiation or with a radical starter dissolved in the polymer [32]. This method is preferentially used when other carriers like titania and zirconia have to be surface modified. Polyethylenimine has been cross-linked at the snrface with pentaerythrolglycidether [41] to yield phases for protein and peptide chromatography. Polysiloxanes can be thermally bonded to the silica surface. Other technologies developed in coating fnsed silica capillaries in GC (polysiloxanes with SiH bonds) can also be applied to prepare RP for HPLC. 

Clark TD, Ghadiri MR. Supramolecular design by covalent capture. Design of a peptide cylinder via hydrogen-bond-promoted intermolecular olefin metathesis. J Am Chem Soc 1995 117 12364-12365. 

M. Hollenstein, C.J. Leumann, Fluorinated olefinic peptide nucleic acid Synthesis and pairing properties with complementary DNA, J. Org. Chem. 70 (2005) 3205-3217. 

R.J. Abraham, S.L.R. Ellison, P. Schonholzer, W.A. Thomas, A theoretical and crystallographic study of the geometries and conformations of fluoro-olefins as peptide analogs. Tetrahedron 42 (1986) 2101-2110. 

Remark-. Preparation of monofluoroalkenes. Monofluoroalkenes are interesting substrates for cyclopropanation and for Diels-Alder reactions." They are also used as a nonhydrolyzable mimic of the peptidic bond (cf. Chapters 3 and 7). The main preparations of fluorinated olefins are as follows ... 

Hydrogen abstraction by ketone sensitizers forms the basis of an elegant alkylation procedure for ethers, amides, lactones, amino acids, and peptides developed by Elad and his group.94 Terminal olefins, for example, can be added to y-butyrolactone (15) in good yield.95... 

Peterson olefination chemistry based upon tert-butyl fluoroacetate, generated in situ from the corresponding bromoester, has also been used in the synthesis of peptide isosteres [ 176,177]. Equation (58) shows the crucial early steps in the synthesis of an inhibitor of Dipeptidyl Peptidase IV. 

Cyanogen Iodide (ICN) has been used extensively for the cyanation of alkenes and aromatic compounds [12], iodination of aromatic compounds [13], formation of disulfide bonds in peptides [14], conversion of dithioacetals to cyanothioacetals [15], formation of trans-olefins from dialkylvinylboranes [16], lactonization of alkene esters [17], formation of guanidines [18], lactamization [19], formation of a-thioethter nitriles [20], iodocyanation of alkenes [21], conversion of alkynes to alkyl-iodo alkenes [22], cyanation/iodination of P-diketones [23], and formation of alkynyl iodides [24]. The products obtained from the reaction of ICN with MFA in refluxing chloroform were rrans-16-iodo-17-cyanomarcfortine A (14)... 

BINAP, 127, 171, 191, 194, 196 olefin reaction, 126, 167, 169, 191 organic halides, 191 Pancreatic lipase inhibitors, 357 Pantoyl lactone, 56, 59 para-hydrogen, 53 Peptides, matrix structure, 350 Perhydrotriphenylene, crystal lattice, 347 Pericyclic reactions, 212 chiral metal complexes, 212 Claisen rearrangement, 222 Diels-Alder, 212, 291 ene reaction, 222, 291 olefin dihydroxylation, 150 Phase-transfer reactions asymmetric catalysis, 333... 

Analogs of cyclic peptides have been prepared using a variety of spacers and reaction conditions to achieve the macrocyclization. These include olefin metathesis (Section 5.2.3), nucleophilic substitution (Sections 8.2 and 7.2.3), and the Heck reaction [82]. 

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