Cyclization experimental procedure

Typical Experimental Procedure (Plate Production). Equal amounts (0.1 mL) of 0.1 M solutions in methanol of the four components are employed generating a theoretical 10 qmol of final product. Reagents were dispensed into a 96-well plate using either a Quadra 96 or Rapid Plate (Zymark) 96-well dispenser. The deprotection/cyclization steps were... 

The cyclization lends itself to the preparation of a number of heterocyclic systems. The reactions are characterized by their good yields, and simple experimental procedure. 

The large variety of different PET-approaches for cyclizations results in a number of specific experimental procedures. Nevertheless, most of these procedures are relatively simple and vary mainly in the photochemical equipment applied and the composition of the starting material. As in any photochemical reaction, certain experimental features must be considered. To circumvent further photodecomposition of the desired product, a suitable wavelength should be selected which avoids absorption by the... 

As the examples mentioned above show, a variety of experimental procedures for cyclizations under dilution conditions exist. Up to this day no generaly applicable procedure is known also, the determination of cyclization parameters to a given target molecule is based on the experiences made by synthesizing similar compounds. Each new structure requires precise conditions for its synthesis often a small window has to be hit with regard to the reaction conditions. 

Cyclizations proceeding by nucleophilic attack at noncarbonyl centers Free radical cyclizations Cycloaddition reactions Experimental Procedures... 

The cycHc urea moiety provides structural rigidity as well as hydrogen-bonding possibihties similar to those of the imidazoles described above. The corresponding 2-imidazolones have been prepared on a soHd phase by tandem aminoacylation of a resin-bound allylic amine with an isocyanate followed by intramolecular Michael addition [73]. However, due to the paucity of data presented on the characterized compounds and the brief experimental procedure, this synthesis is not discussed in detail. Access to cyclic ureas or thioureas has also been obtained by reaction with carbonyl- or thiocarbonyldiimidazole through a cyclo-release mechanism [74—76]. 1,3-Dihydroimidazolones have been obtained by treatment of ureido acetals with TFA and subsequent conversion in an intramolecular cyclization via an N-acyliminium ion [77]. 

In addition, acyclic enantiotopic double bonds can be differentiated by using an asymmetric Heck reaction (Experimental Procedure below typical procedure for desymmetrizing Heck cyclizations). ... 

The Buchwald-Hartwig reaction ( 5.1) can be combined with an intramolecular cyclization i.e., carbopalladation). In particular, an allene can serve as suitable starter molecules see the Experimental Procedure below. "" Depending on the reaction conditions, either the C-N or the C-C coupling proceeds first. 

Alternatively, if the dehydroamino acid is C-terminal or is central in the peptide chain, then the oxazolone precursor to the dehydropeptide must be in position two in order to apply this methodology (Scheme 7.165). The requisite unsaturated 5(4//)-oxazolone intermediate 518 is obtained from the appropriate precursors following standard cyclization procedures and avoiding experimental conditions that would epimerize the chiral center. This methodology has been applied to access analogues of important peptides including dehydroaspartame, somatostatin, and dermorphin. In these cases, a dehydroamino acid was incorporated into the peptide backbone to study the relationship between conformational restriction and biological properties of the modified peptide. 

The synthesis and on-resin cyclization of polycyclic peptides of type I is described in the experimental part of Section 6.8.3.2.3. If side-chain-to-side-chain cyclization is needed the couplings of H-Gly-OFm and Fmoc-Gly-OH should be omitted from that procedure. 

An alternate method for cyclizing ae./i-dihalobutanes is to use a controlled potential electrolytic reduction. 10 12 This method appears to be superior to the conventional reductive cyclization of 1,4-dihalobutanes with metals. Dibromides generally give better results than dichlorides in an aprotic solvent such as dimethylformamide or acetonitrile. Thus, a DC voltage of 1.8-3.0 V was applied for 6 hours to a solution of 1,4-dibromobutane (50 g) in dimethylformamide (1 L) in a cell consisting of a mercury cathode and a nichrome anode, to give cyclobutane and butane in 25 and 75 % yield, respectively.10,11 The experimental setup has been described in a detailed procedure.12... 

Methyl- 1,3-cyclopentanedione is a key intermediate for the total synthesis of steroids.2 A number of methods have been described for its preparation, among them the condensation of succinic acid with propionyl chloride,3 and that of succinic anhydride with 2-buten-2-ol acetate,4 both in the presence of aluminum chloride. It has also been obtained from 3-methylcyclopentane-1,2,4-trione by catalytic hydrogenation5 and Wolff-Kishner reduction 6 The base-promoted cyclization of 4-oxohexanoic acid ethyl ester and diethyl propionylsuccinate with tertiary alkoxides was first reported by Bucourt.7 The present cyclization process provides an experimentally simple route to 2-methyl-1,3-cyclopentanedione. Using the same procedure, 4-oxoheptanoic acid ethyl ester has been cyclized to give 2-ethyl-l,3-cyclopentanedione in 46% yield... 

The stereochemistry of the C-glycosidic products, obtained with the above-mentioned procedure, depends on the structure of the starting sugar and on the experimental conditions. In general, base catalyzed cyclizations afford a mixture of anomers, which on prolonged reaction time is converted into the thermodynamic product. For example, in the case of 4,6-O-isopropylidene-D-glucose,... 

Intramolecular acylation has been used frequently. Houben-Hoesch cyclization of 1 -/ -cyanoethylpyrrole (2a) gives l-oxo-2,3-dihydropyrrolizine (3a).9-17 Difficulties occur because polymerization of the nitrile (2a) can be a side reaction. Addition of boron trifluoride [3a (33%)]11 or its ethyl ether complex [3a (60-80%)]15 has been recommended. Treatment of nitrile 2a with a molten aluminum chloride-potassium chloride-sodium chloride mixture yields 70% of ketone 3a but the experimental conditions are highly critical.13 A reproducible procedure that is based mainly on Clemo s specification9,10 gave 22% of ketone 3a.17 Purification of 3a should be carried out in an efficient fume hood because it appears to induce analgesia.1 ... 

More recently another modification for the preparation of peptide azides was introduced by Alfeeva et al-f l using tetrabutylammonium nitrite as auxiliary reagent. In contrast to the alkyl nitrites which are relatively unstable and therefore have to be purified prior to use by distillation, tetrabutylammonium nitrite is a crystalline and stable compound, which is soluble in anhydrous dipolar aprotic solvents. Moreover, in this procedure the acidity of the reaction mixture is adjusted with anhydrous p-toluenesulfonic acid instead of HCl in anhydrous organic solvents. These conditions are experimentally convenient and more easily controlled than those of the Honzl-Rudinger method. Comparative model reactions performed with ferf-butyl nitrite and tetrabutylammonium nitrite produced nearly identical peptide yields. To date, there are no reports of the condensation of larger fragments and peptide cyclization by this azide procedure. 

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