Internal ester analogue

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

More traditional masking groups have also been used in combination with an internal ester. The acyclic nucleotide analogue based on 2,6-diammopurine has been further modified as its POM (58) and HOP derivatives [112], suggesting that... 

Pd(PPh )2 12 catalyses the internal alkylation of the phosphonate esters (96) and the formation of the 3-methyiene-l-oxa-2-phosphacycl.oalkane 2-oxides (97 ) phosphorus-containing analogues of a-methylenelactones. Further examples of the... 

Bufotenidine or Cinobufagine This is the quaternary amine internal salt, 5-hydroxy-N,N,N-trimethyltryptammonium salt. It also is frequently found as a hydrogen sulfate ester, but this latter has no trivial name. Mention has been made of bufotenidine and its sulfate ester as a occasional companion of histamine analogues found in frog skins. See the appendix on histamines. 

P,y-Diamino analogues 49 of statine are prepared stereoselectively starting from the O-methyl hydroxamate derivative of N-protected statine. The reaction sequence involves the formation of a p-lactam intermediate obtained by internal cyclization under Mitsunobu conditions.184 Alternatively, direct amination of either a p-oxo ester 31 followed by reduction of the resulting enamine 50, 85 or by reduction of the corresponding ,p-unsaturated ester, 88 gives an enantiomeric mixture of the corresponding unprotected p-amine, which is protected by a carbamate prior to chromatographic separation (Scheme 20). 

The chemistry of catharanthine is still being vigorously investigated, in connection with the synthesis of vinblastine and its analogues. Details of some of the earlier work have now become available." New work includes the preparation" of a potentially useful keto-ester (220) from an isoxazolidine derivative (219) obtainable from catharanthine. Hydrogenolysis of (219), followed by allylic oxidation and internal Michael addition, affords (220) as a mixture of C-20 epimers (Scheme 38). Other derivatives include" 15jS-hydroxy-15,20-dihydro-... 

Selective Bu2SnO-catalysed monosulfonylation of methyl a-D-xylopyranoside gave 70% of the substitution at 0-2, while similar sulfonylation of methyl p-D-xylopyranoside gave 90% of the esters at 0-4. TSAO-T 38 and TSAOm -T 39, which have internal sulfonate ester moieties, are potent, selective HIV-I reverse transcriptase inhibitors. New analogues were made by the conversion of the alcohol (40, = OH) to esters, carbamates and thiocarbamates (R =... 

Cl has also been used for the quantitation of diphenoxylic acid (19) in human plasma following the administration of diphenoxylate (18), a drug used in the treatment of diarrhoea (21). The acid was analysed as the methyl ester derivative (20) using the i -analogue as the internal standard (22) (Fig. 8). In this case four ions were selected for monitoring. To compensate for instrument drift the ions at m/e 439.3, 439.4 for methyl diphenyloxalate and m/e 443.3 and 443.4 for the internal standard were chosen. Levels down to 20 ng/ml could be measured. The limit of detection of the gas chromatographic method, previously used... 

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