Synthesis elimination

The chemistry of thiopyrylium salts and their annelated congeners is dominated by the electrophilicity, of the cationic nucleus. Nucleophilic attack is formally the reverse of the principal means of synthesis (elimination of a suitably disposed group), though further reaction can lead to ring cleavage, and, in appropriate cases, to ring closure to alternative heterocycles. 

Unlike the Dakin-West and Henry nitro-aldol methods previously mentioned, the reaction of aldehydes with organometallics has only been used for the synthesis of peptidyl trifluoromethyl ketones. This method, along with the Henry nitro-aldol synthesis, eliminates the use of the toxic reagents required for the Dakin-West synthesis and starts with readily... 

Hydroxyurea inhibits the enzyme ribonucleotide reductase, leading to suppression of DNA synthesis, elimination of cells in the S phase of the cell cycle, and synchronization in the Gj or pre-DNA synthesis phase. The drug is usually administered daily and can be initiated at 40 to 50 mg/kg per day in divided doses until the WBC count falls below 10,000/mm. At that point, the dose can be decreased to a maintenance level of 20 mg/kg per day, but increasingly is tapered and stopped once imatinib therapy is started. Imatinib normalizes blood counts based on suppression of the malignant clone in the bone marrow, an effect not seen with hydroxyurea. Suppression of the malignant clone in the bone marrow is the desired therapeutic effect because of its impact on survival. ... 

Alkenes and Alkynes I Properties and Synthesis. Elimination Reactions of Alkyl Halides 291... 

PROPERTIES AND SYNTHESIS. ELIMINATION REACTIONS OF ALKYL HALIDES 291... 

The structure of the lactone was demonstrated by synthesis. Eliminating a three-atom ethylene oxide ring as improbable, the position of the alkali-resistant 0-acetyl group is located by this evidence as carbon 2. The resistance of this group to alkaline hydrolysis is indicative of an unusual structure. An orthoester structure agrees with this resistance as well as with the ease with which the acetyl and methyl groups are hydrolyzed by acids. The ordinary alkyl orthoacetates exhibit similar properties. 

M. Azori, 1. Szinai, Z. Veres, J. Pato, L. Ostvos, and F. Tudos, Polymeric prodrugs 3. Synthesis, elimination and whole-body distribution of C-labelled drug carrier, Makromol. Chem., 187 (2), 297-302,1986. 

Asymmetric synthesis (eliminative). Optically selective formation of new centers of stable dissymmetry under the intramolecular directing influence of an optically active grouping, the latter being subsequently eliminated from the product. 

An important general method of preparing indoles, known as the Fischer Indole synthesis, consists in heating the phenylhydrazone of an aldehyde, ketone or keto-acld in the presence of a catalyst such as zinc chloride, hydrochloric acid or glacial acetic acid. Thus acrtophenone phenylhydrazone (I) gives 2-phenyllndole (I V). The synthesis involves an intramolecular condensation with the elimination of ammonia. The following is a plausible mechanism of the reaction ... 

Olefin synthesis starts usually from carbonyl compounds and carbanions with relatively electropositive, redox-active substituents mostly containing phosphorus, sulfur, or silicon. The carbanions add to the carbonyl group and the oxy anion attacks the oxidizable atom Y in-tramolecularly. The oxide Y—O" is then eliminated and a new C—C bond is formed. Such reactions take place because the formation of a Y—0 bond is thermodynamically favored and because Y is able to expand its coordination sphere and to raise its oxidation number. 

In the synthesis of molecules without functional groups the application of the usual polar synthetic reactions may be cumbersome, since the final elimination of hetero atoms can be difficult. Two solutions for this problem have been given in the previous sections, namely alkylation with nucleophilic carbanions and alkenylation with ylides. Another direct approach is to combine radical synthons in a non-polar reaction. Carbon radicals are. however, inherently short-lived and tend to undergo complex secondary reactions. Escheirmoser s principle (p. 34f) again provides a way out. If one connects both carbon atoms via a metal atom which (i) forms and stabilizes the carbon radicals and (ii) can be easily eliminated, the intermolecular reaction is made intramolecular, and good yields may be obtained. 

Methylsulfinyl enolates are more recently developed d -reagents. They are readily prepared from carboxylic esters and dimsyl anion. Methanesulfenic acid can be eliminated thermally after the condensation has taken place. An example is found in Bartlett s Brefeldin synthesis (P.A. Bartlett. 1978). 

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

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