Mosher's Acid Research Articles

Improved formal preparation of enantiomerically pure anti-benzo[ a]pyrene diol epoxide

We report an improved, economical formal route to enantiomerically pure anti-benzo[ a]pyrene diol epoxide (BPDE). A trimethylaluminum catalyzed regio- and stereoselective opening of racemic 7,8-epoxy-7,8,9,10-tetrahydrobenzo[ a]pyrene with Mosher's acid delivers benzylic esters exclusively. This step is a significant improvement over the lack of regioselectivity of standard procedures. We also show that modification of the subsequent chemical steps further shortens the preparation of enantiomerically pure anti-BPDE.

Preparation of chlorofluoroacetic acid derivatives for the analysis of chiral alcohols

(R)- and (S)-Chlorofluoroacetic acid (CFA) esters of several Chiral secondary alcohols have been prepared and compared with the corresponding esters of Mosher's acid. CFA itself is a readily accessible and optically stable acid which gives the expected diastereoisomeric products with Chiral alcohols without epimerization. The resulting diastereoisomers are more volatile than those derived from Mosher's acid, and are well resolved by both GC and HPLC. Both 1H and 19F NMR spectra of CFA esters show characteristic signals in regions rarely overlapped by other signals. Since CFA is a strong organic acid, it reacts with alcohols spontaneously to give esters without any additional catalysis.

A Convenient Preparation of (±)-α-Methoxy-α-trifluoromethylphenylacetic Acid (Mosher's Acid)

Abstract Mosher's Acid can be prepared from PhC(O)CF3 via a vinylation, methylation, ozonolysis/oxidation sequence in >80% overall yield.

Enantiospecific syntheses of alpha-(fluoromethyl)tryptophan analogues: interactions with tryptophan hydroxylase and aromatic L-amino acid decarboxylase.

alpha-Fluoromethyl amino acids are enzyme-activated irreversible inhibitors of amino acid decarboxylases. Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible for the final step in the biosynthesis of both dopamine and serotonin via decarboxylation of L-dopa and 5-hydroxy-L-tryptophan, respectively. Our goal is to utilize antagonists of the serotonin-producing enzymes (tryptophan hydroxylase and AADC) as the basis for a chemotherapeutic approach to the treatment of carcinoid tumors, a rare tumor type characterized by the overproduction of serotonin. We report here an enantiospecific synthesis of alpha(S)-(fluoromethyl)tryptophan [(S)-11a] and alpha(S)-(fluoromethyl)-5-hydroxytryptophan [(S)-11b], as well as the (R)-enantiomers, based upon recent methodology involving the face-selective alkylation of cyclic tryptophan tautomers. Our synthetic route provided both enantiomers of 11a and 11b with greater than 97% enantiomeric purity based upon evaluation of the NMR spectra of their Mosher's acid derivatives. (S)-11a was evaluated as a substrate for P815 tryptophan hydroxylase and determined to have an apparent Km of 4.31 +/- 1.07 mM, essentially half the value previously reported for the racemic mixture of 11a with rat brain stem tryptophan hydroxylase. (R)-11a was not a substrate for P815 tryptophan hydroxylase. (S)-11b was evaluated as an enzyme-activated irreversible inhibitor of murine liver AADC and determined to have a KI of 24.3 +/- 3.01 microM and a k2 of 2.26 +/- 0.44 min-1. (R)-11b was not an inhibitor of murine liver AADC.

A new and simple synthesis of Mosher's acid

A new and simple synthesis of Mosher's acid

Silica-bonded chiral stationary phases with structurally simple π-donor chiral selectors for high-performance liquid chromatography

Seven new chiral stationary phases obtained from ( S)-phenylalanine derivatives, ( R)-Mosher's acid and ( S)-naproxen were prepared and evaluated. The racemic substances used to test them contained either π-acidic or π-basic sites. The best results were observed when the chiral entity bonded to γ-aminopropylsilica gel was 3,5-dimethylanilido-, 3,5-dimethylbenzoyl- or 3,5-dimethoxybenzoyl-( S)-phenylalanine and -( S)-naproxen.

Structure of the Mosher's ester derivative of 5-phenyldeltacyclene

Octahydro-5-phenyl-l,2,4-methenopenta- len-6-yl 3,3,3-trifluoro-2-methoxy-2-phenylpropano- ate, C25H23F303, Mr = 428.5, monoclinic, P2~, a = 10.747 (3), b = 7.975 (3), c = 12.435 (5) A, /~ = 92.81 (3) °, V= 1064.5 (12)/~3, Z= 2, Dx = 1.34 g cm -3, ,t(Mo Ka) = 0.71073 A, Iz = 0.98 cm -~, F(000) = 448, room temperature, R = 0.035 for 1523 observed reflections. The X-ray structure determina- tion establishes the relative stereochemistry. The C(sp3)---C(sp 3) bond distances range from 1.492 (6) to 1.554 (5)/~. Experimental. Hydroboration and oxidation of 5- phenyldeltacyclene followed by the reaction of the product alcohol with Mosher's acid chloride gave the desired compound (3).

A simple method for the microscale preparation of mosher's acid chloride

Mosher's acid is treated with oxalyl chloride in the presence of DMF in hexane. Filtration and concentration provide the acid chloride which is suitable for use without further purification. The procedure is amenable to microscale.

Chemoenzymatic preparation of atrolactic and Mosher's acid using Aspergillus oryzae protease

Sterically demanding α-methyl- and α-trifluoromethyl-mandelic esters 5a and 6a were conveniently resolved on a large scale by a protease from Aspergillus oryzae leading to both enantiomers of atrolactic acid 5b and a precursor of Mosher's acid 6b in 75–88% e.e. Single recrystallisation led to optically pure material.

Asymmetric synthesis of primary amines from alkenes and chiral chloronitroso sugar derivatives.

A variety of alkenes 5 - 15, 38, 39 react with chloronitroso sugar derivatives 1 - 3 regioselectively at ambient temperature to give chiral hydroxylamines m 60 - 80% yield. In addition to these products of a formal ene reaction joined by a subsequent hydrolysis 2-substituted hydroxylamines 40 - 49 are also formed. The 2-substituted hydroxylamines 40, 41, 49 possess trans configurations exclusively. The product distribution is solvent dependent and susceptible to the addition of nucleophiles. The reactions employing the reagents 1 and 3 which are approximately mirror images in the vicinity of the chloronitroso function yield opposite enantiomers of the product. Their optical purity was determined by chemical reduction to the amine stage followed by the formation of diastereomeric camphorsulfonic- or Mosher acid amides and subsequent chromatographic or nmr spectrometric analysis. The optical purity for cyclic products was found in excess of 89% ee whereas acyclic alkenes yielded chiral amines in the range of 50 - 90% ee. Chemical degradation and comparison to authentic amino acids confirmed that in every case examined the reaction with the D-mannose derivative 1 yielded the S- configuration at the asymmetric carbon bearing the amino function. The formal ene reactions investigated thus provide another useful EPC synthesis of functionalized chiral amines in acceptable chemical yields and with a predictable stereochemical outcome.

Enantiomeric purity of mosher's acid

Several commercial samples of 2-methoxy-2-phenyl-3,3,3-trifluoropropionic acid (Mosher's acid, MTPA) were investigated for enantiomeric purity by capillary gas chromatography with octakis(3-O-butyryl-2,6-di-O-pentyl)-γ-cyclodextrin as a chiral stationary phase. Enantiomeric purities were found between 97.89 % and 99.80 %.

Enantiomers of mosher's acid chloride first unambiguous determination of their maximum rotatory power

Mosher's acid chloride synthesis may give rise to contaminants depending on the experimental conditions. Correlation between the chemical and chiroptical purity is described.

Stereoisomere Aromastoffe XIX: Asymmetrische Reduktion von 4(5)-Oxocarbonsäuren mit Bäckerhefe / Asymmetric Reduction of 4(5)-Oxocarboxylic Acids by Baker's Yeast

Asymmetric reduction of 4(5)-oxocarboxylic acids (esters) by baker's yeast and cyclization in acidic media yields optically active gamma(delta)-lactones. The evaluation of their chirality and optical purity was carried out by HPLC (HRGC) analysis of the corresponding 1,4(1,5)-diols via diastereomeric esters with (R)-Mosher acid (MTPA) and (S)-O-acyllactic acids respectively. By increasing the 4(5) alkyl side chain 4R(5R) configurated gamma(delta)-lactones with high ee-values are generated.

ChemInform Abstract: Total Synthesis of Natural Estrone and Estradiol Methyl Ethers in Extremely High Enantiomeric Purity via an Asymmetrie Michael Addition to an Unsaturated Sulfoxide.

AbstractThe asymm. Michael addition of the lithium eno1ate(IIa)tothe chiral sulfoxide (IIIa) gives the key intermediate (IVa) in good yield but unsatisfactory se1ectivity in respect of the stereocenter at C‐14 (the degree of asymm. induction is determined via the en‐17‐o1 esters of Mosher acid).

A modified synthesis of mosher's acid and its use in a sensitive stereoisomer analysis of amino acid derivatives

A convenient and sensitive method for stereoisomer analysis of amino acid derivatives is described. It is based on the 19F NMR-analysis of mixtures containing epimers of N-.-methoxy-.-trifluoromethyl-phenylacetyl alanine (MTPA). An improved procedure for the synthesis of MTPA is given.

Direct esterification of α-methoxy-α-(trifluoromethyl)phenylacetic acid

Esters of α-methoxy-α-(trifluoromethyl)phenylacetic acid (Mosher acid, MTPA) were prepared in good yields from alcohols and the free acid Ia using 2-chloro-1-methylpyridinium iodide (II) as condensing agent.

Resolution and absolute configuration of 1,2,3,5,6,10bβ‐hexahydro‐6α‐phenylpyrrolo[2,1‐α]isoquinoline (McN‐4612‐Z). A problem of determination of the enantiomeric purity for a tertiary amine

AbstractDetails for the resolution of 1,2,3,5,6,10bβ‐hexahydro‐6α‐phenylpyrrolo[2,1‐α]isoquinoline (1), a potent antidepressant‐like compound, into its enantiomers with di‐p‐toluoyltartaric acid (2) are reported. Enantio‐merically‐enriched R‐(+)‐2‐phenylpyrrolidine was transformed into enantiomerically‐enriched 1 to determine enantiomeric purity and absolute stereochemistry for the resolved amines 1. Thus, we ascertain that samples of (+)‐ and (—)‐1 with an enantiomeric purity of ≥99% were prepared, and that bioactive (+)‐1 possesses the 6S,10bR absolute configuration. The enantiomeric purity of ≥99% was confirmed by 360‐MHz 1H nmr examination of 1:1 diastereomeric salts formed from 1 or (—)‐1 and (+)‐Mosher's acid (MTPA). The maximal optical rotation reported (ref 8) for (+)‐3 (100% o.p.) was shown to correspond to 100% e.e.