Pure Stereoisomer Research Articles

Energetics of Competing Chiral Supramolecular Polymers.

Chirality can have unexpected consequences including on properties other than spectroscopic. We show herein that a racemic mixture of bis-urea stereoisomers forms thermodynamically stable supramolecular polymers that result in a more viscous solution than for the pure stereoisomer. The origin of this macroscopic property was probed by characterizing the structure and stability of the assemblies. Both racemic and non-racemic bis-urea stereoisomers form two competing helical supramolecular polymers in solution: a double and a single helical structure at low and high temperature, respectively. The transition temperature between these assemblies, as probed by spectroscopic and calorimetric analyses, is strongly influenced by the composition (by up to 70 °C). A simple model that accounts for the thermodynamics of this system, indicates that the stereochemical defects (chiral mismatches and helix reversals) affect much more the stability of single helices. Therefore, the heterochiral double helical structure predominates over the single helical structure (whilst the opposite holds for the homochiral structures), which explains the aforementioned higher viscosity of the racemic bis-urea solution. This rationale constitutes a new basis to tune the macroscopic properties of the increasing number of supramolecular polymers reported to exhibit competing chiral nanostructures.

Analysis of the Stereoisomers (cis, trans) of Polyhedral Oligomeric Silsesquioxane Compounds by UHPSFC-QTof MS

Polyhedral oligomeric silsesquioxanes (POSSs) are a class of important hybrid inorganic/organic materials. When POSSs are used as the building block in polymerization, the materials show superior performance over their organic counterparts in many areas due to the special Si–O cage structure. However, the stereoisomers (cis, trans) of polyhedral oligomeric silsesquioxane (POSS) show some differences in improving polymer property and it is difficult to get the pure stereoisomer by synthesis. Therefore, a method is required to separate and purify the mixture of POSSs. In this study, the isomers of POSS compounds and the impurities were separated by ultra-high performance supercritical fluid chromatography coupled quadrupole time-of-flight mass spectrometry (UHPSFC-QTof MS). To separate the isomers of POSS, the crucial parameters of UHPSFC-QTof MS were investigated. Under the optimal conditions, the isomers of product and impurities were separated in 4 min. On account of exact mass measurement, some impurities were identified. This is the first study on the analysis of isomers of POSS using UHPSFC-QTof MS. Based on this analysis method, it is helpful to optimize the conditions of synthesis.

Crystal Engineering Construction of Caffeic Acid Derivatives with Potential Applications in Pharmaceuticals and Degradable Polymeric Materials.

Natural products are precious feedstock in drug discovery and sustainable materials. This work using crystal engineering strategy, visible light, and solvent-free cycloaddition successfully constructed two caffeic acid derivatives, rel-(1R,2R,3S,4S)-2,4-bis(3,4-dihydroxyphenyl)cyclobutane-1,3-dicarboxylate and rel-(1R,2R,3S,4S)-2,4-bis(3,4-dihydroxyphenyl)cyclobutane-1,3-dicarboxylic acid. Because of the multiple stereocenters, it is challenging to prepare those compounds using traditional organic synthesis methods. The crystal engineering Hirshfeld surface analysis and 2D intermolecular interaction fingerprints were applied to synthetic route design. The light resources used in this work was visible LED or free, clean, and renewable sunlight. The evidence suggested that pure stereoisomer was obtained demonstrating the stereospecificity and efficiency of the topochemical cycloaddition reaction. The derivatives exhibited free radical scavenging and antioxidant biological activities, as well as the potential inhibitory activity of fatty acid binding proteins. One of the derivatives is the precursor of the natural product Shimobashiric acid C which paves the way for the total synthesis and further study of Shimobashiric acid C. In addition, the derivatives possess photodegradability at a specific wavelength, which is very attractive for "green" degradable polymeric materials.

Stereoselective bioactivity, acute toxicity and dissipation in typical paddy soils of the chiral fungicide propiconazole

Propiconazole is a widely used systemic agricultural triazole fungicide with two chiral centers. In the present study, systemic assessments of propiconazole stereoisomers are reported for the first time, including absolute configuration, stereoselective bioactivity toward pathogens (Ustilaginoidea virens, Magnaporthe oryzae, Fusarium moniliforme, Thanatephorus cucumeris, and Rhizoctonia solani), and stereoselective acute toxicity toward aquatic organisms (Scenedesmus obliquus, and Daphnia magna). Moreover, the stereoselective dissipation of propiconazole in three types of paddy soil under laboratory-controlled conditions (aerobic, anaerobic and sterile) was investigated. The degree of bioactivity and acute toxicity of the propiconazole stereoisomers differed depending on the type of target pathogens and non-target organisms. There were 2.43–23.47 and 1.48–2.13 fold differences between the best and worst stereoisomer in bioactivity and toxicity, respectively. Under aerobic conditions, (2S,4S)-propiconazole and (2S,4R)-propiconazole were preferentially degraded in the three types of soils. However, no significant stereoselectivity was observed under anaerobic and sterile conditions. Propiconazole was configurationally stable throughout the study. In comprehensive consideration of bioactivity, toxicity and environmental behavior, using stereoisomer mixture rather than pure stereoisomer may help to control more species of disease in practical application, and the stereoselectivity should be taken into consideration in risk assessment.

Stereoisomeric Composition of Natural Myrtucommulone A.

Myrtucommulone A (MC A) (1), isolated from Myrtus communis (myrtle), shows the same pharmacological activity for inhibition of inflammation and induction of apoptosis as synthetic MC A, which consists of three stereoisomers, i.e., two enantiomers and one meso form. This led to the question of whether the natural MC A is a pure stereoisomer or a mixture of stereoisomers. The specific rotation and electronic circular dichroism (ECD) data of natural MC A (1) as well as of a pentacyclic derivative 4 revealed that naturally occurring MC A (1) consists of the racemate and the meso form in a 1:1 ratio. A probable precursor of MC A (1), nor-semimyrtucommulone (5), was also isolated from myrtle as a racemate. The absolute configurations of the enantiomers of 1 and 5 were determined using a combination of experimental and quantum-chemical calculated ECD spectra.

Application of dimedone enamines as dienophiles: stereoselective synthesis of amino enols of fused uracils containing a sugar moiety by hetero-Diels–Alder reactions of barbituric acid 5-ylidene alditols with dimedone enamines

Dimedone enamines were applied for the first time as new dienophiles in hetero-Diels–Alder reactions with inverse electron demand. Cycloadditions of barbituric acid 5-ylidene alditols with dimedone enamines were performed in dichloromethane at room temperature for 3 days and fused uracils–chromeno[2,3-d]pyrimidine-2,4-diones were obtained in good 73–87% yields. Only one enantiomerically pure stereoisomer was obtained in each studied cycloaddition. Analysis of 1H NMR and 2D NMR spectra allowed for the determination that cycloadducts exist in solution as mixture of the neutral form and dipolar ion. The prepared fused uracils contain both amine and enol functional groups, so share amphiprotic properties and they are zwitterions in solid state. The new class of compounds–amino enols was synthesized, which similarly to amino acids exists as zwitterions. In obtained cycloadducts amino groups and sugar moieties are close each other and they both are in cis configuration and in axial position. It was also shown that different alkenes can be used as dienophiles towards barbituric acid 5-ylidene alditols, for example, styrene or 1-amino-2-thiocarbamoyl-cyclopent-1-ene.

Positional specificity of sardine digestive lipase in the hydrolysis of triacylglycerols and analogs

Using lipid emulsions as well as the monomolecular film technique, we studied some kinetic properties of sardine digestive lipase (SaDL). The pure lipase was able to hydrolyze a triolein emulsion in the absence of any additives and seems therefore to tolerate the accumulation of long free fatty acids at the interface. The kinetic behavior of SaDL can be explained by the high penetration capacity of this enzyme into a lipidic interface. SaDL hydrolyzes efficiently pure tributyrin, in the absence of additives. Subsequently, the sardine lipase is not denaturated at high interfacial energy. A kinetic study of the surface pressure dependency of the regioselectivity of SaDL was performed using an optically pure stereoisomer of diglyceride (1,2‐sn‐dicaprin) and a prochiral isomer (1,3‐sn‐dicaprin) that were spread as monomolecular films at the air‐water interface. At low surface pressure, SaDL acts preferentially on distal carboxylic ester groups of the diglyceride isomer (1,3‐sn‐dicaprin) but at high surface pressure, this enzyme prefers adjacent ester groups of the (1,2‐sn‐dicaprin) isomer. Interestingly, the SaDL was found to hydrolyze efficiently the secondary ester group of a triglyceride analog. This is in line with the fact that SaDL hydrolyzed triolein at the sn‐2 position, as shown using the thin‐layer chromatography technique. This property is sought for the synthesis of specific triacylglycerol‐based compounds, such as structured lipids.Practical applications: The sardine digestive lipase was found to efficiently hydrolyse the secondary ester group of a triglyceride analogue, a characteristic sought for the synthesis of structured lipids.The sardine digestive lipase (SaDL) showed an ability to hydrolyze the secondary ester group of a triglyceride analog (1,2‐DDG) with the R configuration (R3).

Progress in the Synthesis of (−)-α-Kainic Acid

Causing neuronal death, kainic acid and its derivatives are toxic to several known animal species, including rats. Kainic acid and its derivatives have been shown to cause neuroexcitatory activity observed in several neurological disorders. In this research project, a synthetic route that involves control of the stereochemistry to synthesize a pure stereoisomer of kainic acid is proposed. The pure stereoisomer possesses certain medical properties of interest to pharmacological companies. This laboratory synthesis is gaining popularity and increasing importance all over the world because extraction from seaweeds, where kainic acid is found, does not produce reasonable yields. This laboratory procedure will attempt to synthesize kainic acid using an ENE reaction in the final step of the 12 steps as shown in the graphical abstract.

Pyrenylamino Acids: Synthesis, Photophysical and Electrochemical Studies

AbstractSeveral β‐pyrenyldehydroamino acids and a pyrenylalanine derivative have been synthesized in good‐to‐high yields from dehydroamino acids by several types of reactions. A β‐[(pyren‐1‐yl)methylamino]alanine was prepared by treating the methyl ester of N,N‐(di‐tert‐butoxycarbonyl)dehydroalanine with (pyren‐1‐yl)methylamine hydrochloride in the presence of an excess of potassium carbonate. The E isomer of the methyl esters of N‐(tert‐butoxycarbonyl)‐β‐(1,2,4‐triazol‐1‐yl)dehydroalanine and dehydroaminobutyric acid were treated with (pyren‐1‐yl)methylamine hydrochloride in the presence of triethylamine to give the E isomers of the β‐aminomethylpyrene dehydroalanine and dehydroaminobutyric acid derivatives. β‐(Pyren‐1‐yl)dehydrophenylalanine and dehydroaminobutyric acid derivatives were obtained from the pure stereoisomer of the corresponding β‐bromodehydroamino acids and (pyren‐1‐yl)boronic acid by Suzuki cross‐coupling. This reaction was also applied successfully to β‐bromodehydrodipeptides. The electrochemical behaviour of some of the compounds prepared was studied by cyclic voltammetry. The peak potentials for the oxidation and reduction of pyrenylalanines were similar to those reported for pyrene. However, it was found that when the pyrene ring was conjugated with the dehydroamino acid moiety, the compounds had higher oxidation and reduction peak potentials than pyrene. The fluorescence properties of four of the pyrenylamino acids synthesized were evaluated in cyclohexane and alcohols. The methyl ester of N,N‐bis(tert‐butoxycarbonyl)‐β‐[(pyren‐1‐yl)methylamino]alanine presented high fluorescence quantum yields in cyclohexane and ethanol (ΦF = 0.45 and 0.35, respectively). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Synthesis of bis-amino acid derivatives by Suzuki cross-coupling, Michael addition and substitution reactions

Several bis-amino acids were prepared using a bis-Suzuki coupling (compounds 4-8, 10), a sequential Michael addition and bis-Suzuki coupling (compounds 12, 13) and a Michael addition followed by a substitution reaction (compounds 18, 19). Thus, the pure stereoisomer of the methyl esters of N-(tert-butoxycarbonyl)-beta-bromodehydroaminobutyric acid and dehydrophenylalanine and of N-benzyloxycarbonyl-beta-bromodehydroaminobutyric acid were reacted with 1,4-phenylene-bis-boronic acid or 9,9-dioctyl-9H-fluorene-2,7-bis-boronic acid using modified Suzuki coupling conditions. The corresponding bis-dehydroamino acid derivatives were obtained in good to high yields maintaining the stereochemistry of the starting materials. This reaction was also applied successfully to a brominated dehydrodipeptide and 1,4-phenylene-bis-boronic acid showing that it could be used to create cross-links in peptide chains. An N,N-diacyldehydroalanine derivative was used in a sequential Michael addition and bis-Suzuki coupling giving a p-terphenyl bis-amino acid and a fluorenyl bis-amino acid in good yields. Two bis-alpha,beta-diamino acids were obtained by a Michael addition of 1,2,4-triazole to the methyl esters of N-(4-toluenesulfonyl), N-(tert-butoxycarbonyl) dehydroamino acids followed by treatment with ethylenediamine.

Synthesis and Complexation Behaviour of Tetrakis[(N,N-diethylamino-carbonyl)methoxy]tetrahomodioxacalix[4]arene

O-Alkylation of the flexible tetrahomodioxacalix[4]arene 1 with N,N-diethylchloroacetamide in the presence of NaH, K2CO3 or Cs2CO3 gave only one pure stereoisomer, 1,4- alternate-2, while other possible isomers were not observed.

Synthesis and Ion Selectivity of Tetrakis[(N,N-dialkylaminocarbonyl) methoxy]homocalix[4]arenes

An attempted O-alkylation of the flexible macrocycle 1 withN,N-dialkylchloroacetamides in the presence of NaH, K2CO3 or Cs2CO3 gave only one pure stereoisomer 1,4-alternate-2a–c, while other possible isomers were not observed. In contrast, only an intractable mixture was obtained when Na2CO3 was used as base. The structural characterization of these products is discussed. The two-phase solvent extraction data indicated that tetrakis(N,N-dialkylaminocarbonyl) derivatives 2b–c show strong alkali metal cation affinity and the extractabilities are much higher than that for the corresponding calix[4]arene tetraethyl ester 4 and homocalix[4]arene tetraethyl ester 3. High Li+ and Na+ extractabilities were observed for tetrakis[(N,N-diethylaminocarbonyl) derivative 2b. However, no significant high ion selectivity for alkali metal cations was observed in tetraamide 2b. 1H-NMR titration of tetraamide 2b with KSCN clearly demonstrates that a 1:1 complex is formed with retention of theoriginal symmetry to be conformationally frozen on the NMR time scale.

Large-Scale Synthesis of Enantio- and Diastereomerically Pure (R,R)-Formoterol

(R,R)-Formoterol (1) is a long-acting, very potent β2-agonist, which is used as a bronchodilator in the therapy of asthma and chronic bronchitis. Highly convergent synthesis of enantio- and diastereomerically pure (R,R)-formoterol fumarate is achieved by a chromatography-free process with an overall yield of 44%. Asymmetric catalytic reduction of bromoketone 4 using as catalyst oxazaborolidine derived from (1R, 2S)-1-amino-2-indanol and resolution of chiral amine 3 are the origins of chirality in this process. Further enrichment of enantio- and diastereomeric purity is accomplished by crystallizations of the isolated intermediates throughout the process to give (R,R)-formoterol (1) as the pure stereoisomer (ee, de >99.5%).

Synthesis and ion selectivity of conformers of tetraalkyl esters derived from 9,16,25,32-tetrahydroxy[3.1.3.1]metacyclophane

Attempted O-alkylation of the flexible macrocycle 1 with alkyl bromoacetates in the presence of NaH or Cs2CO3 gave only one pure stereoisomer, 3a–c, while other possible isomers were not observed. In contrast, a significant amount of 1,3-O-disubstituted product 2 was produced when Na2CO3 was used as the base. The structural characterization of these products is discussed. The two-phase solvent extraction data indicates that the tetraalkyl esters 3b,c show strong Rb+ affinities comparable with that for 18-crown-6, although the extractabilities are somewhat lower than that for the corresponding calix[6]arene tetraethyl ester 6. A high Rb+ selectivity was observed for tetraethyl ester 3b. However, no significant high ion selectivity was observed with tetramethyl ester 3a. 1H NMR titration of tetra-tert-butyl ester 3c with KSCN clearly demonstrates that a 1:1 complex is formed with retention of the original symmetry that is conformationally frozen on the NMR timescale.

Stereoisomeric flavour compounds LXXVI: direct enantioseparation, structure elucidation and structure-function relationship of 4-tert-butyl-α-methyldihydrocinnamaldehyde

Using enantioselective gas chromatography and heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin (DIAC-TBDMS-β-CD) as the chiral stationary phase, the direct enantioseparation of 4-tert-butyl-α-methyldihydrocinnamaldehyde was achieved. The threshold values and odour characteristics of the enantiomers were investigated by enantioselective gas chromatography/olfactometry. In order to elucidate stereochemical features, the carbonyl-function was oxidized to the corresponding acid and diastereomeric amides were generated with (S)-2-amino-2-phenyl-ethanol [L(+)-α-phenylglycinol] as the enantiopure reagent. After separation and isolation by high-performance liquid chromatography, absolute configurations were deduced from X-ray structure elucidation of a pure stereoisomer. Amide cleavage, reduction and selective oxidation yielded the enantiomers of 4-tert-butyl-α-methyldihydrocinnamaldehyde.

Synthesis and conformational studies of regio- and conformational isomers derived by O-alkylation of tetrahydroxy[3.1.3.1]metacyclophane 1

The synthesis and structure of O-alkylated tetrahydroxy[3.1.3.1]metacyclophanes are described. 6,13,22,29-Tetra-tert-butyl-9,16,25,32-tetrahydroxy[3.1.3.1] metacyclophane 3 was tetra-O-alkylated with alkyl bromides (RBr: R = Et, Pr and Bu) in the presence of Cs 2 CO 3 to yield one pure stereoisomer in each case (i.e. the 1,4-alternate conformer) 5b–d as a major product; other possible isomers were not observed. Ring inversion by oxygen-through-the-annulus rotation is allowed for tetraethoxy and tetrapropoxy derivatives 5b,c (for 5c; coalescence temperature ca. 90 °C) but inhibited for the tetrabutoxy derivative 5d. In contrast, alkyl halides having larger alkyl groups than ethyl afforded poor yields of the corresponding tetra-O-alkylated compounds 5 although a significant amount of 1,3-di-O-substitution products 4 resulted when NaH was used as a base. On the other hand, the tetraol 3 was tetra-O-alkylated with benzyl bromide in the presence of NaH to yield exclusively the cone conformer cone-5f in quantitative yield. Only when the cation-π interactions between the alkali-metal cations and the π-electrons of the benzyl group(s) are able to hold the latter and the oxide group(s) on the same side of the [3.1.3.1]MCP is the conformation immobilized to the cone. The template effect of the sodium cation plays an important role in this benzylation. The 1 H NMR spectral behaviour of these macrocyclic metacyclophanes is also discussed.

Octatjumidylates involving alternating neopentylphosphothionotriester-phosphodiester linkages with controlled stereochemistry at the modified p-center

Starting from each pure stereoisomer of neopentylphosphothionotriester dimer, octathymidylates involving alternating stereoregular neopentylphosphothionotriester-phosphodiester linkages and covalently linked to an acridine derivative at their 3′-end have been synthesized. Their stability towards nuclease degradation was studied by comparison with an octanucleotide-acridine conjugate containing only phosphodiester groups.

Bidentate peptides: Highly potent new inhibitors of enkephalin degrading enzymes

Three series of bidentates bearing an hydroxamic or an N-Acyl-N-hydroxy amino group on structures related to Phe-Gly or Phe-Ala exhibit strong inhibitory potency against purified enkephalinase with IC 50 values in the 4 to 15 nM range. As with thiol-containing inhibitors, such as thiorphan, the most active compounds are those in which a methylene spacer separates the benzyl P 1′ moiety from the Zn coordinating residue. Formation of a bidentate complex with the metal enzyme is clearly demonstrated by a loss of potency of three order of magnitude following the removal of one component of the bidentate group. All the compounds studied are unable to interact with angiotensin converting enzyme (IC 50 > 10,000 nM). Moreover, compounds of the general formula HONHCOCH 2CH(CH 2φ)CONHCH(R)COOH belonging to the most active series of enkephalinase blockers (IC 50 ∼ 4 nM) behave also as highly potent and competitive inhibitors (IC 50 ∼ 10 nM) of a Tyr-Gly releasing dipeptidylaminopeptidase purified from rat brain. The pure stereoisomer [(R)-3-(N-hydroxy) carboxamido-2-benzylpropanoyl]-L-alanine designated kelatorphan, exhibits also a relatively good inhibitory potency against aminopeptidases (IC 50 ∼ 10 μM)f and can be considered as the first virtually complete inhibitor of enkephalin metabolism. This very interesting property of inhibiting all three enzymes of enkephalin metabolism could enhance the required selectivity for a possible clinical use of these inhibitors as new analgesic and psychoactive drugs.

Beta-adrenergic receptors of human leukocytes: studies with intact mononuclear and polymorphonuclear cells and membranes comparing two radioligands in the presence and absence of chloroquine

Owing to the large differences in reported values for β-adrenergic receptor numbers and binding affinity in normal leukocytes, we undertook a systematic re-examination of the binding of two widely used beta antagonists, (-)-[ 3H]dihydroalprenolol (DHA) and (±)- [ 125I]iodohydroxybenzylpindolol (HYP), to intact normal mononuclear (MN) leukocytes and polymorphonuclear (PMN) leukocytes and membrane preparations. Assays were conducted in the presence and absence of chloroquine, which has been proposed recently to eliminate ligand uptake into a non-receptor cell compartment such as lysosomes. The binding curves relating radioligand concentration to specific sitesper intact cell were biphasic. At high (10–24 nM) (-)-DHA ligand concentration in the absence of chloroquine, a large number (20,000–60,000 sites/cell) of low affinity ( K d 12–15 nM) stereospecific binding sites were detected in both cell types. This class of binding sites was eliminated by 10 ,μM chloroquine not only in PMN cells but also in the lysome-poor MN cells (⩾ 90% lymphocytes), leaving 2000–3000 specific high affinity (-)-DHA sites/cell. In the absence of chloroquine, comparably low numbers of specific high affinity binding sites/cell were also obtained by the use of appropriately low concentrations of (-)-DHA or (±)-HYP (800 pM or less). However, even at these low radioligand concentrations chosen to measure high affinity specific binding, the addition of 10 μM chloroquine produced a moderate reduction in the number of sites/cell, without a detectable change in the apparent K d . Mean (± S.E.M.) site numbers obtained in the presence of chloroquine were: 1331 ± 100 sites/MN cell and 1135 ±129 sites/PMN cell ( K d 143–153 pM) using (-)-DHA; and 1487 ± 210 sites/MN cell and 1065 ± 69 sites/PMN cell [avg. K d(±) 224–274 pM] using (±)-HYP. Chloroquine had no effect on agonist-stimulated cAMP production but produced an apparent increase in the effectiveness of (-)-propranolol as an inhibitor of DHA binding. Competition studies on the binding of DHA and HYP with zinterol and practolol confirmed that the receptor was of the β 2-subtype for both MN and PMN cells. The detection of a moderately larger number of high affinity binding sites at saturation (Scatchard analysis) by (±)-HYP than by (-)-DHA was a consistent finding with either intact cells or membranes, with or without chloroquine. The possible overestimation of receptor numbers by a racemic ligand such as (±)-HYP is discussed and leads us to favor the use of a pure stereoisomer such as (-)-DHA. A system employing 800 pM (-)-[ 3H]DHA, 1 ,μM (-)-propranolol and 10, μM chloroquine with intact MN and PMN cells yielded reproducible and plausible results. Our values for β-adrenergic receptor numbers of intact MN and PMN cells and membranes are compared to others in the literature.

Polyfluoro-1,2-epoxy-alkanes and - cycloalkanes. Part II. Reactions of decafluoro-1,2-epoxycyclohexane

The epoxy ring of the title compound has been opened by nucleophilic attack using lithium aluminium hydride, sodium methoxide, methyl lithium, sodium azide and potassium cyanide. The primary product incorporated the nucleophile (N) and an alkoxy function, which was fixed by methylation when N = CN. However, in most cases the alkoxide group decomposed to carbonyl, and the ketone was isolated when N was OMe. More nucleophile could be added across this carbonyl group, the resultant substituted alkoxide being isolated as the tertiary alcohol (N = Me) or the methyl ether (N = N 3). With lithium aluminium hydride (N = H), a secondary alcohol was obtained, the fluorine on the ring carbon bearing the alkoxy group being replaced by H; the pathway probably did not involve a free carbonyl group, since the resultant alcohol was a pure stereoisomer. This was shown by nmr, and also since the pure methoxymethyl ether made from it was dehydrofluorinated exclusively to 2H-octafluorocyclohexenyl methoxymethyl ether.