Alternative approach to synthesis

An alternative approach to synthesis of this ring system involves insertion of CO into the brominated secondary base (43), by treatment with carbon monoxide, lead tetra-acetate, and triphenylphosphine in tributylamine, the product being the amide (44), reduction of which affords the amine.81 Govadine (42 R1 = R4 = OMe, R2 = R5 = OH, R3 = H) has been synthesized by the conventional ring-closure, with formaldehyde, of the diphenolic base (45), or of its dibenzyl ether, in acid solution.82 Tetrahydroberberines, together with N-benzyltetrahydroisoquinolines, have also been obtained by the electrolytic reduction of 3,4-dihydroisoquinolines of structure (46).83... 

All previously described approaches to 3-deoxy-2-ulosonic acids started from advanced carbohydrate precursors, and thus they are not easily applicable to the synthesis of structurally diverse analogues. This concerns chemical syntheses relying on sugar-derived stereocenters and enzymatic ones, providing only very limited access to some naturally occurring compounds. In contrast, de novo syntheses starting from simple, achiral compounds offer much more flexible alternative approaches to synthesis of unnatural ulosonic acid analogues. 

An alternative approach to synthesis of star-shaped polymers or nanoparticles is the use of macromonomers. The Heise group prepared PBLG macromonomers with a styrene endgroup by NCA polymerization initiated with 4-vinylbenzylamine. The macromonomers were then copolymerized with divinylbenzene by free-radical or RAFT polymerization (see Fig. 22). Finally, the peptide block was deprotected to give PGA blocks and resulted in pH-responsive water-soluble nanoparticles [132]. 

An alternative approach to the use of a-aminoketones involves acetals (72JOC221) and pyrazine-2,3-diones have been synthesized by this route (Scheme 58). The acetals are readily available from the phthalimido derivatives via the a-chloroketones. Hemiacetals have also served as a starting point for pyrazine synthesis, although in most cases hemiacetals are too labile to be easily prepared examples are common in the 2-amino-2-deoxy sugar series 2-amino-2-deoxy-D-glucose for example dimerizes to the pyrazine (101) when generated in situ from the hydrochloride salt (68JAP6813469). 

An interesting alternative approach to the synthesis of a cryptand having nitrogen atoms in the bridges was presented by Newkome and coworkers. This group condensed triethanolamine with 2,6-dichloropyridine in a relatively straightforward but low yield (5%) nucleophilic aromatic substitution to form 7, illustrated below in Eq. (8.6). The identity of the compound was confirmed by X-ray structural analysis. 

Corey and co-workers developed an alternate approach to homologation of 6-merabered enones in their synthesis of longifolene. Selective ketaliza-tion of l,6-dioxo-8a-methyl-l,2,3,4,6,7,8,8a-octahydronaphthalene (25) " with... 

An alternative approach to asymmetric synthesis that avoids covalent modification of the substrate is chiral modification of the active reagent. This not only streamlines the number of synthetic manipulations, but it simplifies the isolation of the desired product. In the case of zinc carbenoids, such modifications are feasible alternatives to the use of a standard chiral auxiliary. Two important factors combine... 

The reaction between an aldehyde and a carbon nucleophile, such as a sulfur ylide, constitutes an alternative approach to the synthesis of epoxides. Since alkenes, which are the normal epoxidation substrates, are often formed from aldehydes, this approach can be highly efficient. On the other hand, the synthesis of appropriate carbon nucleophiles usually requires additional steps. 

The novel 6a-A, -thia-l,2,4,6-tetraazapentalenes (82 R = C02Et) was prepared by treatment of the known 1,2,3-thiadiazolino salt (81) with Af-methylbenzimidoyl chloride in pyridine. An alternative approach to the synthesis of tetraazapentalenes (82) via 1,2,4-thiadiazoles will be discussed in section 5.5.3.2 <96BSB335>. 

Samuel Danishefsky s group at the Sloan Kettering Institute for Cancer Research in New York has also been active in the synthesis of the natural epothilones and biologically active analogs. One of their syntheses also used the olefin metathesis reaction (not shown). The synthesis in Scheme 13.62 used an alternative approach to create the macrocycle, as indicated in the retrosynthetic scheme. The stereochemistry at C(6), C(7), and C(8) was established by a TiCl4-mediated cyclocondensation (Step A). The thiazole-containing side chain was created by reaction sequences F and G. The... 

During the same year as Hauser s reported synthesis of calphostin D, the Coleman laboratories published an alternative approach to this family of natural products [32]. This report included the enantioselective syntheses of both phleichrome and calphostin A and, like the previous approaches, started from an enantioenriched naphthalene. 

An alternative approach to the synthesis of 1,3-dienes is by elimination of benzene-sulphinic acid from homoallylic sulphones under basic conditions. This method has been used for the synthesis of a pheromone constituent of the codling moth (equation 67)109. 

An alternative approach to the production of subunit vaccines entails their direct chemical synthesis. Peptides identical in sequence to short stretches of pathogen-derived polypeptide antigens can be easily and economically synthesized. The feasibility of this approach was first verified in the 1960s, when a hexapeptide purified from the enzymatic digest of tobacco mosaic virus was found to confer limited immunological protection against subsequent administration of the intact virus. (The hexapeptide hapten was initially coupled to bovine serum albumin, used as a carrier to ensure an immunological response.)... 

An alternative approach to the spirovetivanes with electrophilic conjunctive cyclopropyl reagents is illustrated in a synthesis of a-vetispirene, 201 (Scheme 11) 139>. 

An alternative approach to the synthesis of internucleotide bonds is to use an insoluble condensing agent, such as poly(3,5-diethylstyrene)sulphonyl chloride.116... 

Because the opportunities for controlled chain growth are more restricted in inorganic than in organic systems, an alternative approach to polymer synthesis becomes appealing. This involves the use of substitution processes carried out on a preformed reactive polymeric intermediate. In this way molecular diversity can be introduced by different substitution reactions rather than by a diversification of the polymerization process. 

Secondly, the quaternised monomer may be replaced with a weakly basic monomer such as MEMA, which exists in its neutral, non-protonated form in alkaline media. Thus the desired zwitterionic block copolymer is prepared in its anionic/neutral form so that no isoelectric point is encountered during the copolymer synthesis. Afterwards, the solution pH can be adjusted to the isoelectric point by the addition of acid to protonate the weakly basic MEMA residues and precipitate the copolymer, which might be a useful alternative approach to column chromatography for the efficient removal of the ATRP catalyst. 

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