Stereochemistry Of Alcohols Research Articles

Stereoselective Synthesis of N‐Propargyl Alkynes and Axial Chiral N‐Allenes with Epimeric Pyrroloimidazolone Auxiliaries

AbstractAn N‐propargyl pyrroloimidazolone with syn stereochemistry derived from L‐proline serves as a starting material for the diastereoselective synthesis (>95:5 dr) of propargyl alkynes or allenamides by direct quench of its lithiated intermediate with alkylating agents or aldehydes/ketones, respectively. Use of the epimeric anti pyrroloimidazolone starting material results in reversal of stereochemistry at the propargyl position in the products, without the need to prepare a separate substrate from D‐proline. Lithiation of the syn pyrroloimidazolone and quench with prochiral benzaldehydes without prior transmetalation gives allenamides with crystallographically verified atypical stereochemistry of the benzylic alcohol in >95:5 dr. The epimeric series of benzylic alcohols may also be obtained in >95:5 dr by employing transmetalation with chlorotitanium triisopropoxide prior to aldehyde quench. Density Functional Theory (DFT) computational studies provide a rationale for the change in benzylic alcohol stereochemistry by virtue of differing stereofacial attack in 6,5‐bicyclic (Li) or 6‐membered (Ti) transition states.magnified image

Chirality Transfer in Au-Catalyzed Cyclization Reactions of Monoallylic Diols: Selective Access to Specific Enantiomers Based on Olefin Geometry

The gold(I)-catalyzed cyclization of monoallylic diols to form tetrahydropyrans is shown to be highly stereoselective when chiral allylic alcohols are employed. Substrates that differ only in olefin geometry provide enantiomeric products from formal S(N)2' reactions in high yields with excellent chirality transfer. The allylic alcohol stereochemistry also efficiently controls the facial selectivity when the substrates include additional stereocenters.

ChemInform Abstract: Structure-Based Design and Synthesis of Substituted 2-Butanols as Nonpeptidic Inhibitors of HIV Protease: Secondary Amide Series.

The design, synthesis, and crystallographic analysis of protein−inhibitor complexes is described for a novel series of nonpeptidic HIV protease (HIV Pr) inhibitors. Beginning with a cocrystal structure of a Phe-Pro peptidomimetic bound to the HIV Pr, design was initiated that resulted in the substituted 2-butanol compound 8 as the lead compound (Ki = 24.5 μM, racemic mixture). Modifications on the initial compound were then made on the basis of its cocrystal structure with HIV Pr and inhibition data, resulting in compounds with enhanced potency against the enzyme (compound 18, Ki = 0.48 μM). These inhibitors were found to bind to the enzyme essentially as predicted on the basis of the original design hypothesis. Stereospecific synthesis of individual enantiomers confirmed the prediction of a binding preference for the S alcohol stereochemistry. Modest antiviral activity was demonstrated for several of the more potent HIV Pr inhibitors in a HIV-1 infected CEM-SS cell line.

Facile synthesis of hydroxy wilfordic acid, a esterifying unit of anti-HIV sesquiterpene pyridine alkaloids

Sesquiterpene pyridine alkaloids were isolated mainly from plants of the genus Tripterygium (Celastraceae) which have been used traditionally in Chinese medicine. These compounds have polyhydroxy dihydro-beta-agarofuran core and esterifying substituent with dilactone bridges, and recently demonstrated promising anti-HIV activity. We have achieved the synthesis of hydroxy wilfordic acid and its ester via asymmetric cyanosilylation. With a NMR study of (S)- and (R)-PGME (phenylglycine methyl ester) amide, the tertiary alcohol stereochemistry of synthetic hydroxyl wilfordic acids was determined. Our synthetic approach will provide a contribution to the synthesis of sesquiterpene pyridine alkaloids and the development of their analogs for anti-HIV activity.

Directed Mutagenesis Alters the Stereochemistry of Catalysis by Isolated Ketoreductase Domains from the Erythromycin Polyketide Synthase

The ketoreductase (KR) domains eryKR(1) and eryKR(2) from the erythromycin-producing polyketide synthase (PKS) reduce 3-ketoacyl-thioester intermediates with opposite stereospecificity. Modeling of eryKR(1) and eryKR(2) showed that conserved amino acids previously correlated with production of alternative alcohol configurations lie in the active site. eryKR(1) domains mutated at these positions showed an altered stereochemical outcome in reduction of (2R, S)-2-methyl-3-oxopentanoic acid N-acetylcysteamine thioester. The wild-type eryKR(1) domain exclusively gave the (2S, 3R)-3-hydroxy-2-methylpentanoic acid N-acetylcysteamine thioester, while the double mutant (F141W, P144G) gave only the (2S, 3S) isomer, a switch of the alcohol stereochemistry. Mutation of the eryKR(2) domain, in contrast, greatly increased the proportion of the wild-type (2R, 3S)-alcohol product. These data confirm the role of key residues in stereocontrol and suggest an additional way to make rational alterations in polyketide antibiotic structure.

Conserved amino acid residues correlating with ketoreductase stereospecificity in modular polyketide synthases.

Getting down to specifics: Key amino acid residues were found to correlate with ketoreductase domain stereospecificity in modular polyketide synthases. These residues may allow alcohol stereochemistry (see scheme; ACP, acyl carrier protein) in polyketides to be predicted from ketoreductase sequences. The results also suggest that polyketide synthase dehydratase domains have a preference for 3hydroxyacyl substrates with the same alcohol stereochemistry as the (3R)-hydroxyacyl chains used by dehydratases in fatty acid synthases. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2003/z581_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Determination of the absolute stereochemistry of alcohols and amines by NMR of the group directly linked to the chiral derivatizing reagent

NMR experiments and calculations (PM3) indicate that the asymmetry of the substrate (alcohol or amine) leads to the redistribution of the conformer populations of their methoxyphenylacetic acid (MPA) or methoxytrifluoromethylphenylacetic acid (MTPA) derivatives rather than to the distortion of the conformer geometry as was postulated by Mosher. An absolute configuration of secondary alcohols and primary amines can be determined according to the chemical shifts of the CαH protons in NMR spectra of their MPA derivatives. The CαH proton of the diastereomer having a greater relative population of the sp form should resonate at a lower field.

Enantioselective hydrolyses of α-methylated cyclohexyl acetates by the cultured cells of Marchantia polymorpha

A high enantioselectivity was observed in the hydrolyses of racemic α-methylated cyclohexyl acetates with the cultured cells of Marchantia polymorpha. The enantiomeric excesses of alcohols obtained in the hydrolyses were correlated with the torsional angles between the acetoxyl and α-methyl groups. They have made it possible to predict the optical purity as well as the absolute stereochemistry of alcohols hydrolyzed by using the cultured cells of M. polymorpha.

Alcohol Stereochemistry in Polyketide Backbones Is Controlled by the β-Ketoreductase Domains of Modular Polyketide Synthases

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTAlcohol Stereochemistry in Polyketide Backbones Is Controlled by the β-Ketoreductase Domains of Modular Polyketide SynthasesCamilla M. Kao, Michael McPherson, Robert N. McDaniel, Hong Fu, David E. Cane, and Chaitan KhoslaView Author Information Departments of Chemical Engineering Chemistry, and Biochemistry Stanford University Stanford, California 94305-5025 Department of Chemistry, Box H, Brown University Providence, Rhode Island 02912 KOSAN Biosciences, Inc., 1450 Rollins Road Burlingame, California 94010 Cite this: J. Am. Chem. Soc. 1998, 120, 10, 2478–2479Publication Date (Web):February 27, 1998Publication History Received17 November 1997Published online27 February 1998Published inissue 1 March 1998https://doi.org/10.1021/ja973913aCopyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views562Altmetric-Citations71LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (51 KB) Get e-AlertsSUBJECTS:Alcohols,Metabolism,Peptides and proteins,Redox reactions,Stereochemistry Get e-Alerts

D-ring allyl derivatives of 17β- and 17α-estradiols: Chemical synthesis and 13C NMR data

We report the 13C NMR data for 17β-estradiol, 17α-estradiol, and a series of ten 17β- or 17α-estradiol derivatives bearing an allyl group on the D-ring (at C-17, C-16, and C-15 positions). The target 17β-OH estradiol derivatives were synthesized from estrone by well known methods to ensure the accuracy of the allyl stereochemistry. The 17α-estradiol derivatives were obtained by a modified Mitsunobu alcohol inversion of 17β-analogs. The carbon assignments were done using 1D and 2D NMR experiments. Six positions of the allyl group (17α, 17β, 16α, 16β, 15α, and 15β) and two alcohol stereochemistries (17β and 17α) of the D-ring were studied, resulting in an important source of data. The effect of allyl-positioning and alcohol stereochemistry on 13C NMR chemical shifts was also identified, producing important points of comparison for other steroid analogs.

Structure-based design and synthesis of substituted 2-butanols as nonpeptidic inhibitors of HIV protease: secondary amide series.

The design, synthesis, and crystallographic analysis of protein-inhibitor complexes is described for a novel series of nonpeptidic HIV protease (HIV Pr)inhibitors. Beginning with a cocrystal structure of a Phe-Pro peptidomimetic bound to the HIV Pr, design was initiated that resulted in the substituted 2-butanol compound 8 as the lead compound (Ki = 24.5 microM, racemic mixture). Modifications on the initial compound were then made on the basis of its cocrystal structure with HIV Pr and inhibition data, resulting in compounds with enhanced potency against the enzyme (compound 18, Ki = 0.48 microM). These inhibitors were found to bind to the enzyme essentially as predicted on the basis of the original design hypothesis. Stereospecific synthesis of individual enantiomers confirmed the prediction of a binding preference for the S alcohol stereochemistry. Modest antiviral activity was demonstrated for several of the more potent HIV Pr inhibitors in a HIV-1 infected CEM-SS cell line.

Ionic addition mechanism investigation. Determination of deuterated nortricyclyl alcohol stereochemistry

Ionic addition mechanism investigation. Determination of deuterated nortricyclyl alcohol stereochemistry

542. Triterpenoids. Part LV. The stereochemistry of alcohols derived from glutinone (alnusenone)

542. Triterpenoids. Part LV. The stereochemistry of alcohols derived from glutinone (alnusenone)