MTPA Esters Research Articles

Stereostructural studies on the 4-hydroxylated annonaceous acetogenins: A novel use of Mosher ester data for determining relative configuration [between C(4) and C(36)

Analysis of MTPA (Mosher) esters of model butenolides 7 vs. the MTPA derivatives of 4-hydroxylated acetogenins provides the first general method for assignment of C(4)/C(36) relative configuration.

Determination of absolute configuration of α-hydroxyphosphonates by 31P NMR spectroscopy of corresponding mosher esters

( R)-MTPA esters of α-hydroxyphosphonates 1a-h of known absolute configuration were prepared and their 31P NMR spectra were recorded. The chemical shifts of the 31P signals of the derivatized ( S)-alcohols are consistently downfield relative to the signals of the corresponding ( R)-alcohols. A variety of racemic and diastereomeric α-hydroxyphosphonates 1i-o and their ( R)-MTPA esters were prepared. The 31P chemical shift differences are large enough to securely assign absolute configurations to α-hydroxyphosphonates.

Absolute stereochemistry of non-adjacent bis-tetrahydrofuranic acetogenins

Absolute stereochemistry of non-adjacent bis-tetrahydrofuranic acetogenins has been established by comparison of the 1H-NMR data of their MTPA esters with those of optically active model tetrahydrofurans. 12 R, 15 S, 16 S, 19 R, 20 R, 23 R, 24 S configuration was assigned for squamostatins-B and -D, whereas 12 R, 15 S, 16 S, 19 R, 20 R, 23 R, 24 R configuration was assigned for squamostatins-C and -E.

Biosynthesis of (10R)‐Juvenile hormone III from farnesoic acid by Aedes aegypti ovary

AbstractSynthesis of (10R)‐juvenile hormone III (JH III) outside the corpora allata (CA) was investigated in female Aedes aegypti. Intact females or ligated abdomens of blood‐fed and sugar‐fed females synthesized in vivo [12‐3H]JH III‐like molecules from [12‐3H]‐methyl farnesoate, indicating that an organ(s) in the female abdomen, other than the CA, converted methyl farnesoate into JH III. To find out the organ(s) that synthesized JH III‐like molecules, ovaries, fat bodies, and midguts were incubated in vitro with [12‐3H]methyl farnesoate and the synthesis of JH III‐like molecules was compared with JH III synthesized by CA. To identify tissue(s) having both farnesoic acid methyl transferase and farnesoate epoxidase, enzymes that convert farnesoic acid into JH III, ovaries, and fat bodies were removed from sugar and blood‐fed females and incubated with [12‐3H]farnesoic acid. Chemical derivatization by methoxyhydrin formation followed by esterification with (+)‐α‐methoxy‐ α‐trifluoromethyl phenylacetic (MTPA) acid chloride and reversed phase liquid chromatography identified (10R)‐JH III methoxyhydrin (+)‐MTPA ester as the sole JH III‐like molecule produced in tissue culture incubation of ovaries. Since only (10R)‐JH III is produced and not racemic JH III, the oxidation of farnesoic acid must be enzymatically mediated. Ovaries and corpora allata of female A. aegypti also synthesized [3H,14C]JH III from L‐[methyl‐3H]methionine and [14C]acetate which was characterized by HPLC and gas chromatography. These results suggest that mosquito ovary can synthesize (10R)‐JH III from farnesoic acid, and that this tissue synthesizes JH III‐like molecules from L‐methionine and acetate. © 1994 Wiley‐Liss, Inc.

Absolute stereochemistry of petroformynes, high molecular polyacetylenes from the marine sponge Petrosia ficiformis

The absolute stereochemistry of some petroformynes ( 1-7), characteristic metabolites of the Mediterranean sponge Petrosia ficiformis displaying terminal 1-yn-3-ol-4-ene moieties, has been elucidated by applying high field 1H-NMR to Mosher method. Esterification of Petrosia polyacetylenes with ( R)- and ( S)-α-methoxy-α-trifluoromethylphenylacetyl (MTPA) chloride yielded the corresponding ( S)- and ( R)-MTPA esters. Careful NMR measurements led to assign the S absolute stereochemistry at all the chiral centers of petroformynes. The R absolute stereochemistry of 3-hydroxydocosa-4( E), 15( E)-dien-1-yne ( 8), previously established on the basis of a questionable extention of the application of the exciton chirality method, is confirmed by applying advanced Mosher method. The structures of petroformyne-5 ( 7) and petroformyne-8 ( 11) are now supported by additional evidence.

Chemical synthesis of the (1R,2S) and (1S,2R) arene oxide metabolites of acridine

Enantiopure samples of (+)-(1R,2S) and (–)-(1S,2R)-1,2-epoxy-1,2-dihydroacridine 4 have been obtained from the corresponding trans-2-bromo-1,2,3,4-tetrahydroacridin-1-ol MTPA esters 7a and b. Absolute configurations were deduced by stereochemical correlation to (+)-(1R,2R)-trans-2-bromo-1-(2-methoxy-2-phenyl-2-trifluoroacetoxy)-1,2,3,4-acridine 7a which was unequivocally assigned by X-ray crystal structure analysis. (–)-(1R,2R)-trans-1,2-Dihydroacridine-1,2-diol 2 was obtained by alkaline hydrolysis of (+)-(1R,2S)-acridine 1,2-oxide 4.

Resolution of prenyl bromohydrin esters and derivatives: synthesis of the quinoline alkaloid (+)-(R)- and (−)-(S)- lunacridine

Chromatographic separation of the bromohydrin MTPA diastereoisomers formed at the prenyl group attached to quinoline and coumarin rings is reported; base catalysed cyclization of the bromo MTPA esters in the quinoline series yielded the corresponding prenyl epoxide enantiomers. This provides a synthetic route to the enantiopure quinoline alkaloid lunacridine 11 and to the dihydrofuroquinoline 8-methoxy-platydesmine 8.

Enantioselective synthesis of cinnamyl-1-phenyl-2-propenyl ether: A metabolite of marine green algal species caulerpa racemosa

The enantioselective synthesis of title compound has been achieved using a new enzyme acyl system and a mild PT catalysed etherification. The absolute configuration of natural compound has been established as R-(+) by 1HNMR analysis of MTPA esters of the intermediate carbinols.

Determination of the absolute configuration of chiral secondary alcohols; new advances using 13C- and 2D-NMR spectroscopy

The use of 1H- 13C and 1H- 1H 2D COSY correlation experiments substantially enhances the potential of the NMR procedure for determining the absolute configuration of chiral secondary alcohols via their diastereomeric MPA and/or MTPA esters. Phenyl ring current effects are observed over remarkably long distances and comparable effects are seen for both 13C and 1H chemical shifts. The use of 13C chemical shifts to aid configurational assignment is particularly valuable.

An intramolecular cyclization approach to optically active cyclopentenyl bromides

The two antipodes of 1-bromo-3,3-dimethyl-4-[(tert-butyldimethylsilyl)oxy] cyclopentene, the dextrorotatory form of which (1) is regarded as a potential synthetic precursor to kalmanol, have been prepared in a state of high enantiomeric purity from propargyl alcohol. The key steps in the abbreviated synthetic pathway involve the bromination-dehydrobromination of 3-(trimethylsilyl)propenal 12 to give 2-bromo-3-(trimethylsilyl)propenal 7, the conversion of 2-bromo-3-(trimethylsilyl)propen-1-ol 13 to the 1-bromo-3,3-dimethylcyclopenten-4-ol 18 by a novel tandem Claisen-Sakurai reaction sequence, and efficient enzymatic resolution of 18 via its chloroacetate ester. The absolute configurational assignments are based on 1 H NMR analyses of the (R)- and (S)-MTPA esters of (-)-20

On the unusual propensity by the red seaweed Laurencia microcladia of II Rogiolo to form C15 oxepanes: Isolation of rogioloxepane A, B, C, and their likely biogenetic acyclic precursor, prerogioloxepane

AbstractIt is shown here that the red seaweed Laurencia microcladia KÜTZNING, collected in the Mediterranean off the torrent Il rogiolo, contains the C15 acetogenin rogioloxepane A ( = (+)‐(2R,7R)‐2‐(1‐bromopropyl)‐7‐[(Z)‐1‐chlorohex‐3‐en‐5‐ynyl]‐2,3,6,7‐tetrahydrooxepin; (+)‐3) besides its epoxy derivative rogioloxepane B ((+)‐4) and the rogioloxepane C ((+)‐5) derived from (+)‐4 by epoxide opening. Co‐occurring is an acyclic C15 acetogenin, perrogioloxepane ( = (7R,4Z,9Z,12Z)‐6‐chloropentadeca‐3,9,12‐trien‐1‐yn‐7‐ol; 9), which exists preferentially in a folded conformation as required to give, by intramolecular cyclization, rogioloxepane A (3TC) in its favored twist‐chair form. Molecular‐mechanics calculations support this view and help also to assign the relative configurations at the side chains, whereas the configurations at the seven‐membered ring are established via NMR spectroscopy and chemical correlations. The absolute configuration is established by Mosher's NMR method applied to the MTPA esters of (+)‐5 or 9.

Highly enantioselective synthesis of (–)-chokol A

Stereoselective introduction of a methyl group into the (3S)-2-methylcyclopentanone 3, followed by Claisen rearrangement of the vinyl ether 10 derived from the allyl alcohol 7 provided separable methyl esters 6a and 6b. Reduction of 6a and subsequent homologation of the side-chain afforded the pivaloyl ester 16 after protection of the primary alcohol 15 with pivaloyl chloride. Cleavage of the double bond of compound 16, followed by sodium borohydride reduction of the resultant aldehyde 17, produced a mixture of the diols 18 and 19 leading to (–)-chokol A 5. Its enantiomeric excess was determined based on examination of the 1H NMR spectrum of its MTPA ester 25.

Determination of the Absolute Configuration and Enantiomeric Purity of Allylic and Acetylenic Alcohols

Abstract The relative magnitude of steric bulk of saturated vs. unsaturated substituents in the title compounds has been estimated by a lanthanoid induced shift (LIS) study of these (R)-(+)-α-methoxy-α-(trifluoromethyl)phenylacetate esters [(R)-(+)-MTPA esters] by 1H NMR spectroscopy: CH2=C(Me)−>Pentyl>n−Pr>Et\simeqCH2=CH−>Me>CH≡C−;Ph>Cyclohexyl These results allow the assignment of the absolute configurations of both cyclic and acyclic unsaturated alcohols. Furthermore, the relative intensity of well-separated OMe signals for those diastereomeric MTPA esters can be used for the determination of the %ee of the original alcohols.

A short highly regio- and stereoselective synthesis of triacylglycerols

Glycidyl esters reacted with carboxylic anhydrides in the presence of LiBr in tetrahydrofuran (THF) or benzene to produce 3-bromo-1,2-propanediol esters with no significant acyl migration. Displacement of Br by cesium carboxylates was accomplished cleanly in THF-hexamethylphosphoric triamide (THF-HMPT) at 50–55°C (5 h) completing a highly regioselective triglyceride synthesis. The regioselectivity of these reactions allows stereoselective synthesis if one initiates the short sequence with enantiomerically pure glycidol. Commercial ( R)-(+)-glycidol (94.6% R) was used to synthesize ( R)- and ( S)-lauroyl oleoyl palmitoyl glycerol. 1H-NMR data of S-methoxy- α-trifluoromethylphenyl acetic acid (( S)-MTPA) derivatives formed by reaction of the (S)-MTPA ester of ( R)-glycidol indicated that these reactions preserved configuration as expected.

Absolute Configuration of Sipholenol-A. Presence of Two Conformers of MTPA Ester Moiety in a Crystalline State

Abstract Absolute configuration of sipholenol-A was established as (4S) by a single crystal X-ray analysis of its (S)-(−)-MTPA ester. Two conformers of the MTPA ester moiety were recognized as an occupancy of 0.5:0.5 in crystalline state; the positions of the groups can be rationalized by van der Waals interactions to nearest molecules.

Oxime ethers as potential juvenoids: Synthesis of optical isomers

AbstractTwo racemic juvenoids 5 and 6 and their optical isomers 10, 11, 17 and 18 having chiral centres in the aliphatic side chain were synthetized. The second chiral centre in the molecules remained racemic in all derivatives prepared. The absolute configurations of the optically active centres of the enantiomers were determined on the basis of the 1H‐NMR spectral evaluation of the diastereoisomeric MTPA esters 12, 13, 19 and 20 derived from the intermediate alcohols 8 and 15. The optical purity was established by an HPLC analysis of the corresponding MTPA esters. The 1H‐NMR spectra of all compounds as well as the CD spectra of all chiral isomers were measured and discussed.

ChemInform Abstract: Direct Esterification of 2‐Methoxy‐2‐phenyl‐3,3,3‐trifluoropropionic Acid: A Reinvestigation.

AbstractIn the previously reported direct esterification of the enantiomeric title compounds (I) (MTPA) (activated by reagent (II) in the presence of DMAP), the ratio of the corresponding diastereomeric MTPA esters did not correspond to the actual proportion of enantiomers in the studied mixtures.

The substrate- and stereoselectivity of microbial reductions of 1,4-dithiaspiro[4.5]decanones and 1,5-dithiaspiro[5.5]undecanones

The title spirocyclic ketones, possessing possible substitution patterns 1,4-dithiaspiro[4.5]decan-6-one (1a), -7-one (3a), and -8-one (5a), and 1,5-dithiaspiro[5.5]undecan-7-one (2a), -8-one (4a), and -9-one (6a), have been reduced with new strains of yeast (Saccharomycescerevisiae, JCM 1819 and JCM 2214). Reductions of the prochiral ketones 1a–4a occur with high enantiofacial selectivity on the preparative scale (up to 99% ee). The product alcohols (1,4-dithiaspiro[4.5]decan-6-ol (1b) and -7-ol (3b) and 1,5-dithiaspiro[5.5]undecan-7-ol (2b) and -8-ol (4b)) have the S configuration, as confirmed by 2D COSY experiments of the (S)-MTPA esters of 1b–4b using the configuration correlation model of Mosher. Keywords: microbial reduction, Saccharomycescerevisiae, dithiaspiro ketones, substrate- and stereoselectivity, H,H-COSY spectra.

Determination of the absolute configuration and enantiomeric purity of alcohols from the 13C‐NMR spectra of the corresponding MTPA esters

AbstractFrom a study of the 13C‐shift values of the MTPA esters of 3‐substituted cyclohexanols of known absolute configuration an empirical rule has been developed to determine the absolute configuration of chiral cyclohexanols. The method is based on the Dale–Mosher model, which was originally developed for 1H‐NMR spectra. The scope and limitations of this method are discussed. The enantiomeric purity of the alcohols can be determined simultaneously by integration of the signals in well‐resolved diastereotopic carbon pairs.

High-performance liquid chromatographic separation of 11-hydroxylauric acid enantiomers : Application to the determination of the stereochemistry of microsomal lauric acid (ω-1) hydroxylation

Racemic 11-hydroxylauric acid was obtained in a two-step synthesis and derivatized to diastereoisomeric ( S)-α-methoxy-α-trifluoromethylphenylacetate esters of methyl 11-hydroxylaurate, which were readily resolved by isocratic normal-phase high-performance liquid chromatography (HPLC). The assignment of absolute configuration of each diastereoisomer was carried out using proton NMR spectroscopy and a lanthanide shift reagent. From this result, an analytical method was designed for the determination of the stereochemical outcome of (ω — 1) lauric acid hydroxylation mediated by rat liver microsomes. 14C-labelled ω- and (ω — 1)-hydroxylated lauric acids were separated by reversed-phase HPLC and quantified by liquid scintillation counting. Enantiomeric (ω — 1)-methyl laurates were derivatized into their diastereoisomeric ( S)-MTPA esters, resolved and quantified by HPLC. Some typical inducers of cytochrome P-450 were used and their effects on lauric acid hydroxylase activity, regioselectivity and stereoselectivity were shown.