Glycals in stereochemical synthesis

Enantiomerically pure (14R)-14-methylhexadeca-8Z-enal (cis-trogodermal) — the aggregation pheromone of the khapra beetle (Trogoderma) — and its (14S,8Z)-enantiomer has been effected from di-O-benzoyl-D- and -L-arabinals.     

Glycals in stereochemical synthesis

Enantiomerically pure (14R)-14-methylhexadeca-8Z-enal (cis-trogodermal) — the aggregation pheromone of the khapra beetle (Trogoderma) — and its (14S,8Z)-enantiomer has been effected from di-O-benzoyl-D- and -L-arabinals.Institute of Chemistry, Bashkir Branch, Urals Branch, Russian Academy of Sciences, Ufa. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 707–712, September–October, 1991.     

Fluorogenic stereochemical probes for transaldolases

Transaldolase catalyzes the transfer of dihydroxyacetone from, for example, fructose 6-phosphate to erythrose 4-phosphate. As a potential probe for assaying fluorescent transaldolase, 6-O-coumarinyl-fructose (1) was prepared in six steps from D-fructose. The corresponding 6-O-coumarinyl-5-deoxy derivative 2 was prepared stereoselectively from acrolein and tert-butyl acetate by a chemoenzymatic route involving Amano PS lipase for the kinetic resolution of tert-butyl 3-hydroxypent-4-enoate (7) and E. coli transketolase for assembly of the final product. The corresponding stereoisomer related to D-tagatose was obtained by a chemical synthesis starting from D-ribose. Indeed, transaldolases catalyze the retro-aldolization of substrate 1 to give dihydroxyacetone and 3-O-coumarinyl-glyceraldehyde. The latter primary product undergoes a beta-elimination in the presence of bovine serum albumin (BSA) to give the strongly fluorescent product umbelliferone. A similar reaction is obtained with the 5-deoxy analogue 2, but there is almost no reaction with its stereoisomer 3. The stereoselectivity of transaldolases can be readily measured by the relative rates of fluorescence development in the presence of the latter pair of diastereomeric substrates.     

The stereochemical course of bromoetherification of enynes

Enynes undergo stereoselective syn intramolecular bromoetherification; the stereochemical course of the reaction was elucidated by X-ray crystallographic studies and by stereospecific synthesis of authentic bromoallenes.     

Synthesis and stereochemical assignment of (+)-chamuvarinin

A stereocontrolled total synthesis of (+)-chamuvarinin, isolated from the root extract of Uvaria Chamae, utilizes a convergent modular strategy to construct the adjacently linked C15-C28 ether array, followed by a late-stage Julia-Kocienski olefination to append the butenolide motif. This constitutes the first total synthesis of (+)-chamuvarinin, defining the relative and absolute configuration of this unique annonaceous acetogenin.     

Maximizing the stereochemical diversity of spiro-ladder oligomers

[reaction: see text] We introduce all stereoisomers of a bis-amino acid building block derived from trans-4-hydroxy-L-proline. This small library of monomers allows arbitrary stereochemical configuration at any chiral center within our spiro-ladder oligomers. Three tetramer oligomers containing several combinations of the monomers 1-4 were synthesized; we explored the effect of monomer sequence on scaffold conformation by NMR.     

Some stereochemical aspects of the pellizzari rearrangement

Variable temperature nmr spectroscopy and X-ray crystallography have been employed to study the stereochemistry of 2-cyano-3,3-dimethyl-1-phenylpyrazolidin-5-one which thermally rearranges to 2,3-dihydro-2,2-dimethylpyrimido[1,2-a]benzimidazol-4(1H)-one.     

Outer-ring stereochemical modulation of cytotoxicity in cephalostatins

[structure: see text] 20- and 25'-epimers of cephalostatin 7, prepared by directed unsymmetrical pyrazine synthesis, address outer-ring topographical and stability questions and intimate an oxacarbenium ion rationale for the role in bioactivity of the spiroketal (E/F, E'/F') rings of this class of antitumor agents.     

Rigid cyclophanes that illustrate stereochemical principles

All of the point groups common to organic chemistry except two are illustrated by known compounds that are rigid [2.2]paracyclophane derivatives. Examples are given of transannular directing effects by acetyl, nitro, and acetoxyl substituents attached to [2.2]paracyclophane. In bromination or chloromethylation, proton loss of a sigma complex is rate-determining, and the oxygens already in the molecule remove the proton being substituted. The synthesis of [2.2.2](1,2,4)cyclophane and [3.2.2](1,2,5)cyclophane, and their unusual chemical properties are described. Transannular hydride shifts out of methyl groups due to proximity effects are reported. Torsional racemizations and epimerizations of [2.2]paracyclophane derivatives are reviewed. The diradical intermediates formed have been intercepted by either H· donors, or by addition to substituted olefins. To account for the stereochemical course of addition and substitution reactions in the side-chains of [2.2]- and [4,2]paracyclophanes, new types of bridged carbonium ions are suggested. Conformational equilibria in the four-carbon side-chain of [4.2]paracyclophane derivatives are discussed.     

Synthesis and stereochemical assignment of brasilibactin A

[structure: see text] Brasilibactin A, a naturally occurring siderophore related to the mycobactins, has been synthesized in six steps. Use of asymmetric titanium-mediated aldol reactions allowed the preparation of both diastereomers from a common synthetic intermediate, thus allowing the relative stereochemistry of the natural product to be assigned. Brasilibactin A exhibits no inhibition of histone deacetylases (HDACs) in spite of the N-formyl-N-hydroxy lysine moiety that is expected to affect the activity of these metal-dependent lysine-modifying enzymes.     

Absolute stereochemical determination of chiral carboxylic acids

Monoamidation of 1,4-diaminobenzene with alpha-chiral carboxylic acids leads to a carrier strategy for absolute stereochemical determination with bis-zinc porphyrin tweezers by exciton-coupled circular dichroism (ECCD). The helicity induced in the porphyrin tweezers upon complexation with the derivatized carrier originates from the preferred conformation of the C(carbonyl)-C(chiral) bond. Correct ECCD signs can be predicted by the rotamer that places the large group perpendicular to the carbonyl group with the small group facing the porphyrin. [reaction: see text]     

Selective HOESY experiments for stereochemical determinations

Heteronuclear Overhauser effect spectroscopy (HOESY) is a powerful method for tracking geometrical proximities between two heteronuclei (for instance, (1)H and (13)C, as this will be the case here). The method is based on cross-relaxation arising from dipolar interactions. Sensitivity permitting, it is applied in the 2D mode yielding all spatial correlations in a single experiment. Whenever sensitivity is not sufficient, it can be applied in the one-dimensional mode by selectively inverting one particular proton. In that case, it yields, from the carbon-13 spectrum, remote spatial correlations. The method has been employed here for the discrimination between two possible E or Z isomers in a medium-size molecule.     

A stereochemical study of optically active thiazolidines

We report a stereochemical study of a series of free N-H and N-methylated 1,3-thiazolidines bearing H or CH₃ at C-(2). These compounds were readily prepared from ephedrine and pseudoephedrines. The stereochemistry of the compounds under study was deduced using ¹H and ¹³C NMR spectroscopy. Two isomers were found for compounds having a methyl group at C-(2) (i.e. C-(2)HCH₃); interconversion of these isomers, presumably via a non-cyclic zwitterionic intermediate, was observed.     

Propellanes as substrates for stereochemical studies

Various reactions are described in which the behavior of configurationally-different propellanes may be correlated with the respective configurations.     

Regio- and stereochemical aspects of bromochlorination of norbornene

Bromochlorination of norbornene whose chemo- and regio-selectivity is determined by the type of the halogenating reagent used was studied. Three isomeric bromochloronorbornanes (2-endo-bromo-3-exo-chloro-, 2-exo-bromo-3-endo-chloro-, and 2-exo-bromo-7-syn-chlorobicyclo[2.2.1.]heptanes), 2-exo-7-syn- and 2-exo-7-anti-dibromo- and-dichloronorbornanes, and 2-bromonortricyclane were isolated and characterized by¹H and¹³C NMR spectra. The spectral and structural characteristics of the resulting compounds are discussed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2290–2295, November, 1998.     

Enantioselective synthesis and stereochemical revision of communiols A-C

Enantioselective synthesis of the proposed structure of communiol C, an antibacterial tetrahydrofuran derivative produced by Podospora communis, and its stereoisomers revealed that the genuine stereochemistry of communiol C should be 3R, 5R, and 6S. Two other structurally related metabolites of the same microbial origin, communiols A and B, were also synthesized based on the revised stereochemistry.