2- Azabicyclo octane- 3 -carboxylic

ABOCA, 2-azabicyclo[3,3,0]octane-3-carboxylic acid. DBOSA, dibenzyloxysuccinic acid anhydride. [S-M-H-H20]+/[S-H]+ value. 

The initial medicinal chemistry route to the azabicyclo[3.3.0]octane-3-carboxylic acid produced the azabicyclo system in a diastereoselective but racemic manner, and required a classical resolution to achieve enantioenriched material (Teetz et al., 1984a, b 1988). Reaction of (R)-methyl 2-acetamido-3-chloropropanoate (43) and 1-cyclopentenylpyrrolidine (44) in DMF followed by an aqueous acidic work-up provided racemic keto ester 45 in 84% yield (Scheme 10.11). Cyclization of 45 in refluxing aqueous hydrochloric acid provided the bicyclic imine, which was immediately reduced under acidic hydrogenation conditions. The desired cis-endo product 46 was obtained upon recrystaUization. The acid was protected as the benzyl ester using thionyl chloride and benzyl alcohol, providing subunit 47 as the racemate. Resolution of 47 was accomplished by crystallization with benzyloxy-carbonyl-L-phenylalanine or L-dibenzoyl-tartaric acid. 

Hoechst has reported an enantioselective approach toward the key azabicyclo[3.3.0] octane-3-carboxylic acid 46 that preserves the stereochemistry of the L-serine-derived starting material (Urbach and Henning, 1991). L-Serine methyl ester (48) was alkylated... 

In an extension to this work, treatment of the template with 5-hexynal under the standard dehydrating conditions furnished the cycloadduct 301 in good yield (68). However, structural analysis of both the product and the azabicyclo[3.3.0]octane-3-carboxylic acid, derived by hydrogenation of the double bond, followed by... 

The preparation of a chiral bicyclic hydrazine, (15,35,5S)-2-amino-3-methoxymethyl-2-azabi-cyclo[3.3.0]octane (SAMBO, 3), was reported32 in 1990. (12 S, 31 S,51 5 )-2-Azabicyclo[3.3.0]-octane-3-carboxylic acid was resolved into its enantiomers. The (lS ,35,55)-enantiomer was converted to the chiral hydrazine 3 in six steps, utilizing Hofmann degradation, which is also employed in the preparation of SAMP. 

Dansyl amino acids (li ,3R,5R)-2-Azabicyclo-[3,3,0]-octane-3-carboxylic acid 115... 

AZABICYCLO(3.2.1)OCTANE-2-CARBOXYLIC ACID, 3-(BENZOYLOXY)-8-METHYL-, PROPYL ESTER,HYDROCHLORIDE (lR-(2-endo.3-exo))-... 

A solution of 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-l,4-benzoxazine-8-carboxylic acid in tetrahydrofuran and dimethylformamide is cooled to below 0°C and triethylamine is added under stirring thereto. Further, ethyl chlorocarbonate is added and the mixture is stirred at room temperature. To the resultant mixture is added 3-amino-8-azabicyclo[3.2.1]octane and the mixture stirred. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, washed with water and dried over magnesium sulfate. The solvent is distilled off to give 6-chloro-3,4-dihydro-4-methyl-N-(8-azabicyclo[3.2.1]oct-3-yl)-3-oxo-2H-l,4-benzoxazine-8-carboxamide. 

Chemical Name (3S)-2-((2S)-N-((lS)-l-Carboxy-3-phenylpropyl)alanyl)-2-azabicyclo[2.2.2]octane-3-carboxylic acid, (1-ethyl ester)... 

Tropisetron (Trap C17H20N2O2 MW 284.15 g/mol CAS-No 89565-68-4 (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octane-3-yl lH-indole-3-carboxylate). 

Converting enzyme (ACE) inhibitors 176) likewise prevent the formation of angiotensin II and are used in the treatment of renal and essential hypertension. Examples of orally active ACE-inhibitors are (2)-l-[(2S)-3-[N-(S)-mercapto-2-methylpro-panoyl]proline170) (captopril 77), l-[N-(S)-l-carboxy-3-phenylpropyl]-L-alanyl-L-proline-1 -ethyl ester177 (enalapril 78), and 2-[N-[(S)-l-ethoxycarbonyl-3-phenyl-propyl]-L-alanyl]-(lS,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid178) (Hoe 498 79). 

Hajdu P, Schmidt D, Bomm M, Keller A (1984) Determination of (2-[N-[(S)-l-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid) (HOE 498) and its hydrolysis product in serum and urine. Arznm Forsch/Drug Res 34 1431-1435 Schmidt D, Keller A (1985) Sensitive determination of the ACE-Inhibitor HOE 498 and its metabolites in human urine by capillary GC. Fresenius Z Anal Chem 320 731 Walle T, Ehrsson H, Bogentoft C, Dolby J (1972) Synthesis and structure of an enaminic bis(trifluoroacetyl) derivatives of desipramine. Acta Pharm Suecica 9 509-512... 

Ifenprodil (= l-Methyl-2-hydroxy-2-(4-hydroxyphenyl) ethyl-1 -(4-benzyl-piperidine)] -(aryl piperidine) [at(/o-3-(Indol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane] (indolotropane) [Kynurenic acid (= 4-Hydroxy-2-quinolinecarboxylic acid)] (quinoline carboxylic acid) [Memantine (= 1-Amino-3,5 dimethyladamantane)] (amino adamantane, amino cyclic aliphatic) [Methadone (= 6-Dimethylamino-4,4-diphenyl-3-heptanone)] (aryl tertiary amine) [em/o-3-(l -Methylindol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane(indolotropane) exo- 3-( 1 -Methylindol-2-yl)-8-methyl-8-... 

Kolbe reactions of heterocyclic compounds have been studied in only a few cases. Anodic oxidation of l-azabicyclo[2.2.2]octane-2-carboxylic acid under Kolbe conditions produced 2-methoxy-l-azabicyclo[2.2.2]octane [454]. The primary radical, formed by loss of an electron from the carboxylate ion, decarboxylates and is oxidized further to a carboca-tion, which is attacked by a methoxide ion. A similar pseudo-Kolbe reaction is found in the anodic decarboxylation of 1,2,3,4-tetrahydroisoquinoline-l-carboxylic acid derivatives to 3,4-dihydroisoquinolines [455]. 

P-Cocaine 2P-carbomethoxy-3-p-benzoxytropane, methyl [lR-(cjro,exo)]-3-(benzoyloxy)-2-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate [50-36-2] M 303.4, m 98°, b 187-188°/0.1mm, [a]p -15.8° (c 4, CHCI3), pK 8.39. Crystallises from EtOH and sublimes below 90° in a vacuum in a non-crystalline form. 

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