Use of shift reagent with MTPA derivatives in 1H NMR spectroscopy. III. Determination of absolute configuration and enantiomeric purity of primary carbinols with chiral center at the C-2 position

Yasuhara, Fujiko; Yamaguchi, Shozo

doi:10.1016/s0040-4039(01)83433-x

Cited by 27 publications

(11 citation statements)

References 14 publications

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“…To determine the absolute configurations of 6 and 7 , we employed the method of Yamaguchi and Yasuhara for determination of the absolute configurations of primary alcohols with the asymmetric center at the 2-position 16. In this approach, an acyclic alcohol is converted to the corresponding ( R )-(+)-MTPA and ( S )-(-)-MTPA esters.…”

Section: Resultsmentioning

confidence: 99%

Pulicatins A−E, Neuroactive Thiazoline Metabolites from Cone Snail-Associated Bacteria

et al. 2010

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The cone snail Conus pulicarius from the Philippines provides a specific habitat for actinomycetes and other bacteria. A phenotypic screen using primary cultures of mouse dorsal root ganglion neurons revealed that one C. pulicarius associate, Streptomyces sp. CP32, produces a series of natural products that enhance or diminish whole-cell Ca 2+ flux. These compounds include known thiazoline compounds and a series of new derivatives, pulicatins A-E (6-10). Individual compounds were shown to bind to a series of human receptors, with selective binding to the human serotonin 5-HT 2B receptor. Here, we report the structure elucidation of the new compounds and results of the neurological assays.Symbiotic bacteria living with animals have been implicated in the synthesis of defensive and other natural products of importance to drug discovery.1 -5 In the marine environment, most studies of symbiont-derived natural products have focused on soft-bodied, benthic invertebrates that are otherwise vulnerable to predation. By contrast, cone snail mollusks are well defended by their shells and their arsenal of extremely diverse, snail-derived peptide toxins that act on channels and receptors.6 We sought to investigate whether this type of well-defended organism would also house symbiotic bacteria involved in the synthesis of allelochemicals, potentially including venom components, antibacterial defenses, and other small-molecule natural products. In addition to investigating this basic question, we reasoned that exploration of an untapped bacterial niche could lead to the discovery of new bioactive natural products.We recently reported that at least some cone snails are associated with diverse actinomycetes and other bacteria, and that extracts of some of these bacteria exhibit neurological activity.7 In order to maximize the discovery of new active bacterial metabolites from these new niches, we applied a broad-scope assay involving primary * Corresponding author. Mailing address: College of Pharmacy, Medicinal Chemistry, 307 Skaggs Hall, 30 S. 2000 E., Rm. 201, Salt Lake City, Utah 84112-5820. Tel: (801) 585-9119. ews1@utah.edu. Supporting Information Available: NMR data for pulicatins A-E (6-10), DRG assay results, application of LIS, 1 H NMR of MTPA esters for compounds 1, 6 and 7, HRESIMS data of compounds 1 and 6-10. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public Access Results and DiscussionExtracts of pilot-scale cultures of strain CP32 were strongly active in the DRG assay, resulting in K + -stimulated Ca 2+ influx. CP32 was fermented in 2.8 L Fernbach flasks for eight days. In an assay-guided procedure, the culture broth was centrifuged and subjected to HP20 adsorption chromatography, followed by C 18 flash chromatography and HPLC to yield compounds 1-10.A known compound, aerugine (1) was isolated as a pale yellow solid.10 , 11 The NMR and low resolution MS data also exactly matched a siderophore compound (1a) isolated from a bacterium associated with a marin...

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Section: Resultsmentioning

confidence: 99%

Pulicatins A−E, Neuroactive Thiazoline Metabolites from Cone Snail-Associated Bacteria

et al. 2010

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“…In the present study, we examined the relation between the absolute configuration and oxymethylene proton chemical shifts in the MTPA esters of simple primary alcohols (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) with a C2-branched methyl. Like the case of compounds 1-7, if the differences between Dd S and Dd R are relatively large (Ͼ0.10 ppm) they allow the assignment of the absolute configurations at the oxymethine carbons at C2.…”

Section: Resultsmentioning

confidence: 99%

“…1,4) Although attempts to assign the absolute stereochemistry of C2-chiral primary alcohols using its MTPA esters have been demonstrated, there is no conventional method applicable for a limited amount of natural products. 5) Minale and coworkers have applied a Mosher's method for determination of absolute stereochemistry of a methyl group at C25 of steroids with a primary hydroxyl group at C26, 6,7) and reported that the proton signals of the methylene (C26) attached to the ester linkage in the MTPA derivatives showed a unique split pattern as follows. In the 1 H-NMR spectra of the (ϩ)-(R)-MTPA esters, two 26-methylene protons of the 25S isomer were much closer [Dd(d low Ϫd high ) ca.…”

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confidence: 99%

Application of Modified Mosher's Method for Primary Alcohols with a Methyl Group at C2 Position.

Tsuda

Toriyabe

Endo

et al. 2003

CHEMICAL & PHARMACEUTICAL BULLETIN

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Modified Mosher's method using a-methoxy-a-trifluoromethylphenylacetyl (MTPA) esters has been recognized as a useful and reliable method for determination of absolute configurations of secondary alcohols and primary amines. [1][2][3] The absolute configurations at such methine carbons could be determined by the regular arrangement: positive and negative chemical shift differences [Dd(d S Ϫd R )] of the protons can be found on the right and left sides of the MTPA plane, respectively. Nevertheless, it is difficult to assign the absolute configurations of tertiary and primary alcohols since of the irregular arrangements of the Dd values. 1,4) Although attempts to assign the absolute stereochemistry of C2-chiral primary alcohols using its MTPA esters have been demonstrated, there is no conventional method applicable for a limited amount of natural products. 5) Minale and coworkers have applied a Mosher's method for determination of absolute stereochemistry of a methyl group at C25 of steroids with a primary hydroxyl group at C26, 6,7) and reported that the proton signals of the methylene (C26) attached to the ester linkage in the MTPA derivatives showed a unique split pattern as follows. In the 1 H-NMR spectra of the (ϩ)-(R)-MTPA esters, two 26-methylene protons of the 25S isomer were much closer [Dd(d low Ϫd high ) ca. 0.04] to each other than those (Dd ca. 0.14) of the 25R isomer, whereas in the (Ϫ)-(S)-MTPA esters, the mutual relation was reverse. During our studies on stereochemistry of marine natural products, [8][9][10][11][12] we have applied this method for primary alcohols with a branched methyl at C2, and proposed the absolute configurations at chiral centers attached to the methyl group. For example, the absolute configuration at C14 of amphidinolide T1 was elucidated on the basis of chemical shift differences and signal patterns of the geminal protons at C13 of (S)-and (R)-MTPA esters of the C13-C21 segment 10) (Fig. 1). The methylene protons of C13 for the (R)-MTPA ester were observed as separated double doublet signals at d H 4.03 and 4.26 (Dd 0.23), while those for the (S)-MTPA ester appeared at d H 4.09 and 4.12 (Dd 0.03), indicating that absolute configuration at C14 was R. However, this methodology has not been substantiated by examination of compounds with known stereochemistry. Recently, we have applied this method for a series of primary alcohols with a C2-branched methyl whose stereochemistry is known. In this paper we describe the scope and limitation of this methodology on the basis of the present results. Results and DiscussionA series of primary alcohols (1-14) with a methyl group (Chart 1), whose absolute configurations are known, were synthesized or obtained commercially, and they were converted into the corresponding (S )-and (R)-MTPA esters. Chemical shifts of the oxymethylene protons in the (S)-and (R)-MTPA esters of each alcohol in CDCl 3 were shown in Table 1 The absolute configurations of a series of primary alcohols possessing a branched methyl group at C2 position were examined o...

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“…The lanthanide-induced shifts in the spectra of MTPA derivatives of primary alcohols chiral at the b-position correlated with absolute configuration. 56 The distinction of primary alcohols with remotely disposed chiral centers can be achieved using (1R,2R)-2-(anthracene-2,3-dicarboximido)cyclohexane carboxylic acid. The anthryl ring is positioned to shield a considerable portion of the alcohol as shown in Figure 3.…”

Section: Ddmentioning

confidence: 99%

Assignment of absolute configuration using chiral reagents and NMR spectroscopy

2010

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Use of shift reagent with MTPA derivatives in 1H NMR spectroscopy. III. Determination of absolute configuration and enantiomeric purity of primary carbinols with chiral center at the C-2 position

Cited by 27 publications

References 14 publications

Pulicatins A−E, Neuroactive Thiazoline Metabolites from Cone Snail-Associated Bacteria

Pulicatins A−E, Neuroactive Thiazoline Metabolites from Cone Snail-Associated Bacteria

Application of Modified Mosher's Method for Primary Alcohols with a Methyl Group at C2 Position.

Assignment of absolute configuration using chiral reagents and NMR spectroscopy

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