Richard K. Hill

Magnetic non-equivalence of methylene protons in dissymmetric benzylamines : A simple method of assignment of configuration to identically α,α′-disubstituted heterocyclic bases

Abstract As a result of the lack of a plane of symmetry in identically α,α′- trans -disubstituted heterocyclic amines, the methylene protons of their N-benzyl derivatives are stereochemically and magnetically non-equivalent. The resultant splitting in the NMR spectrum enables an easy differentation between cis and trans isomers.

An approach to natural 2-alkyl-6-methylpiperidines via N-acyllactam rearrangement

Abstract Application of the Mundy N-acyllactam rearrangement to 6 - methyl - 2 - piperidone has led to a synthesis of optically active dihydropinidine, confirming the absolute configuration of the pine alkaloid pinidine, and to a new synthesis of the fire ant toxin, Solenopsin A.

The absolute configuration of methyl jasmonate

Abstract The absolute configuration of the jasmine oil constituent methyl jasmonate has been determined. Methyl dihydrojasmonate was synthesized from (−) 3-oxocyclopentaneacetic acid, whose configuration was established by three independent methods: (a) ORD comparison with 3-methylcyclopentanone, (b) synthesis from optically active norcamphor, and (c) synthesis from (−) cyclopent-2-eneacetic acid.

The chemistry of zerumbone. Part 5: Structural transformation of the dimethylamine derivatives

Abstract Zerumbone ( 1 ) and its 6,7-epoxide ( 2 ) react with ammonia and dimethylamine regio- and stereospecifically, affording monoamines 3 , 4 , 7 and 8 . All adducts have the same relative configuration at C2 and C3. The conjugate amination is thermodynamically controlled to arrive at a single diastereomer. At 15°C 7 reacts with cyanide to give aminonitrile 10 as the single product, while at 30°C, acyclic aminonitrile 11 is also formed. The reaction with 8 affords at 0°C bicyclic aminonitrile 12 of the asteriscane skeleton, while at 30°C or higher temperature, mixtures of 12 and tricyclic nitriles 13 and 13′ are obtained. Refluxing of 7 , 8 and 10 in aqueous acetonitrile promotes scission of the zerumbone ring by retro-Mannich reaction to provide acyclic aldehydes 16–18 , respectively. The dimethylamino group of 7 , 8 and 10 is eliminated stereospecifically by Cope- and base-catalyzed eliminations to regenerate the zerumbone skeleton in the products 1 , 2 and 21 . Cope elimination of 12 results in a mixture of 13 and 13′ by deaminative transannular etherification.

Stereochemistry of the jaborandi alkaloids

Abstract The relative configurations of pilocarpine and isopilocarpine, the major alkaloids of jaborandi leaves, have been established as cis and trans, respectively. Degradation of their oxidation product, homoisopilopic acid, to an optically active 2,3-diethylbutane-1,4-diol proves the trans sterochemistry of the iso series. Assignment of absolute configuration is based on (a) conversion of homoisopilopic acid to (2R:3R) 2,3-diethyl-γ-butyrolactone and (b) interrelation of isopilopic acid with R(+)-ethylsuccinic acid.

Stereochemistry of valine and isoleucine biosynthesis: IV. Synthesis, configuration, and enzymatic specificity of α-acetolactate and α-aceto-α-hydroxybutyrate☆

Abstract A new synthetic route, involving acetylenic intermediates, has been developed for the preparation of the valine and isoleucine biosynthetic intermediates α-acetolactic acid ( III ) and α-aceto-α-hydroxybutyric acid ( IV ) including the optically active form of these labile acids. The absolute configuration of acetolactate methyl ester XV was confirmed as (R)-(−), and the configuration of XVI was also established as (R)-(−). Two trideuterio analogs of acetolactate were prepared by this route. The acetolactate anion was found to undergo a rapid room-temperature degenerate rearrangement resulting in racemization and methyl interchange. The isomeroreductase of Salmonella typhimurium was found to be specific for the (S) enantiomers of III and IV , allowing conclusions about the conformation of IV during the ethyl migration step in isoleucine biosynthesis. Acetolactate decarboxylase of Acidobacterium aerogenes was found to decarboxylate specifically the (S) enantiomers of III and IV , forming (−)-acetoin from III with inversion of configuration.

The stereochemistry of pinidine

Abstract The stereochemistry of pinidine, a piperidine alkaloid from Pinus sabiniana, was established by chemical and spectroscopic methods as 2-(R)-methyl-6-(R)-(2-trans-propenyl)-piperidine (XXI). Some interesting rearrangements which occurred during degradative studies are discussed, and the configuration of pinidine is compared with that of related alkaloids.

Cope, Oxy-Cope and Anionic Oxy-Cope Rearrangements

The Cope rearrangement,1 discovered in 1940 by Arthur C. Cope early in his outstanding career, comprises the thermal rearrangement of 1,5-dienes to isomeric 1,5-dienes (equation 1). Today it is recognized as the prototype all-carbon member of a large family of related rearrangements which include the Claisen, aza-, thia- and phospho-Claisen rearrangements, rearrangements of allylic esters, and a number of other variations collectively classified as 3,3-sigmatropic rearrangements.

Stereochemistry of ammonia elimination from l-tyrosine with lphenylalanine ammonia-lyase

Abstract The trans stereochemistry was established for the enzymatic deamination by l -phenylalanine ammonia-lyase from Rhodotorula texensis, based on the spectroscopic analysis of the deamination products from stereospecifically labeled l -(3R)-[3- 2 H 1 ] - and l -(3S)-[2,3- 2 H 1 ]tyrosine used as substrate. The exchange of hydrogen on C-2 was not observed during the ammonia-elimination process.

Stereochemistry of valine and isoleucine biosynthesis II. Absolute configuration of (−)α,β-dihydroxyisovaleric acid and (−)α,β-dihydroxy-β-methylvaleric acid☆

Abstract The valine biosynthetic precursor (−)α,β-dihydroxyisovaleric acid has been converted to (S) (+)-2,3-dihydroxy-2-methylbutane, demonstrating that the dihydroxy-acid intermediate has the (R) configuration. The corresponding isoleucine precursor, (−)α,β-dihydroxy-β-methylvaleric acid, has been degraded to (R) (−)-2-hydroxy-2-methylbutyric acid, establishing the (R) configuration at C-3; the natural intermediate is consequently the (2R;3R) isomer. The stereochemistry of the enzymatic reactions involving these intermediates is discussed.