Dess-Martin Periodinane Oxidation Research Articles

Catalytic [2+2+2] Tandem Cyclization with Alkyl Substituted Methylene Malonate Enabling Concise Total Synthesis of Four Malagasy Alkaloids

Catalytic [2+2+2] Tandem Cyclization with Alkyl Substituted Methylene Malonate Enabling Concise Total Synthesis of Four Malagasy Alkaloids

Asymmetric Total Synthesis of Phomarol

Asymmetric Total Synthesis of Phomarol

First total synthesis of the pro-resolving lipid mediator 7(S),12(R),13(S)-Resolvin T2 and its 13(R)-epimer

The first total synthesis of the pro-resolving lipid mediator 7(S),12(R),13(S)-Resolvin T2 [7(S),12(R),13(S)-RvT2] and its 13(R)-epimer, derived from n-3 docosapentaenoic acid (n-3 DPA), are described. 7(S),12(R),13(S)-RvT2 and its 13(R)-epimer were obtained by total synthesis using a chiral pool strategy to introduce the chiral centers. C7 was generated from S-(−)-1,2,4-butanetriol in both molecules and the C12 and C13 centers were generated from L-(+)-ribose and D-(−)-arabinose respectively. Cis and trans-selective Wittig reactions, selective deprotections, and Dess-Martin periodinane oxidation were the key steps in the syntheses.

Simultaneous targeted and untargeted UHPLC-ESI-MS/MS method with data-independent acquisition for quantification and profiling of (oxidized) fatty acids released upon platelet activation by thrombin

In this study, a combined targeted/untargeted UHPLC-ESI-QTOF-MS/MS method for the targeted quantitative analysis of the primary platelet lipid mediators thromboxane B2 (TXB2), 12S-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) and its oxidation product 12-keto-5Z,8E,10E-heptadecatrienoic acid (KHT) was developed, which allowed simultaneous untargeted profiling for the detection of other lipid biomarkers such as other oxylipins and fatty acids (FAs) in platelet releasates. A general procedure for the synthesis of keto-analogs from hydroxylated polyunsaturated FAs (PUFAs) using Dess-Martin periodinane oxidation reagent was proposed for the preparation of KHT standard. MS detection was performed in data independent acquisition (DIA) mode with sequential window acquisition of all theoretical fragment ion mass spectra (SWATH) in the range of 50–500 Da with variable window sizes. The LC-MS/MS assay was validated for the targeted analytes and applied for analysis of supernatants derived from resting platelets and from platelets treated with thrombin. The targeted analytes KHT, HHT and TXB2 were found at highly elevated levels in the activated platelet releasates. On average, 13 ± 7, 15 ± 9, and 0.6 ± 0.2 attomols per platelet were released upon thrombin-activation. Furthermore, the simultaneous untargeted profiling (n = 8 in each group) revealed that these oxylipins are released with a pool of other (significantly upregulated) oxidized (12-HETE, 12-HEPE) and non-oxidized PUFAs. All these compounds can be considered additional biomarkers of platelet activation complementing the primary platelet activation marker thromboxane B2. The other lipids may support platelet activation or trigger other biological actions with some potential implications in thromboinflammation.

Stereoselective Synthesis of Northern Fragment of Eribulin Mesylate from d-Mannose

Stereoselective synthesis of northern fragment of eribulin mesylate is reported by coupling of the C1–C13 fragment with the C28–C35 fragment. The key steps involved in this synthesis are butyllithium-facilitated coupling between sulfone and aldehyde, then Dess–Martin periodinane oxidation followed by samarium(II) iodide mediated desulfonylation.

One-pot preparation of labelled mannan-peptide conjugate, model for immune cell processing.

An efficient method for preparation of fluorescently labelled mannan-peptide glycoconjugates has been developed. After selective Dess-Martin periodinane oxidation of mannan, it was conjugated to the fluorescent label alone and a peptide with the label via reductive amination. Prepared glycoconjugates were characterised by HPSEC, FTIR-ATR and UV-VIS spectroscopy. Finally, the fluorescently labelled mannan and mannan-peptide conjugate were used for microscopic visualization of their accumulation in intracellular organelles of RAW 264.7 cells.

Total synthesis of 3-epi-(+)-lycoricidine from Garner aldehyde via intramolecular aldol cyclization

A highly efficient total synthesis of 3-epi-(+)-lycoricidine has been described for the first time from easily available (S)-Garner aldehyde with an overall yield of 7% in 20 steps. Stereoselective nucleophilic addition, Sharpless asymmetric dihydroxylation, Dess–Martin periodinane oxidation, intramolecular aldol cyclization, and Luche reduction are the salient features of this approach.

Concise Total Synthesis of Helicascolides A, B, and C

The concise total synthesis of helicascolides A, B, and C has been achieved in seven steps starting from commercially available tiglic aldehyde [( E )-2,3-dimethylacrylaldehyde]. Oppolzer’s sultam aldol, Mukaiyama aldol, and Dess–Martin periodinane oxidation reactions are the key steps involved in the target synthesis.

Syntheses of Chiral 1,8‐Cineole Metabolites and Determination of Their Enantiomeric Composition in Human Urine After Ingestion of 1,8‐Cineole‐Containing Capsules

AbstractThe chiral metabolites in human urine were investigated after ingestion of a 1,8‐cineole (eucalyptol)‐containing entero‐coated capsule (Soledum). For identification of the various enantiomers the enantiomerically pure (−/+)‐α2‐hydroxy‐1,8‐cineole, (−/+)‐β2‐hydroxy‐1,8‐cineole, (−/+)‐9‐hydroxy‐1,8‐cineole, and (−/+)‐2‐oxo‐1,8‐cineole were prepared. To achieve this aim, after acetylation of the synthesized racemic 2‐ and 9‐hydroxy‐1,8‐cineoles, pig liver esterase‐ or yeast‐mediated hydrolysis provided the (−)‐alcohols with their antipodal (+)‐acetates with enantiomeric excess of 33–100 %. Dess–Martin periodinane oxidation of the alcohol (+)‐α2‐hydroxy‐1,8‐cineole, obtained by hydrolysis of the resolved acetate, provided the corresponding (+)‐2‐oxo‐1,8‐cineole, meanwhile the oxidation of (−)‐α2‐hydroxy‐1,8‐cineole gave (−)‐2‐oxo‐1,8‐cineole. Using these standards seven metabolites (+/−)‐α2‐hydroxy‐1,8‐cineole, (+/−)‐β2‐hydroxy‐1,8‐cineole, (+/−)‐α3‐hydroxycineole, (+/−)‐3‐oxo‐1,8‐cineole, 4‐hydroxy‐1,8‐cineole, 7‐hydroxy‐1,8‐cineole, and (+/−)‐9‐hydroxy‐1,8‐cineole, all liberated from their glucuronides, were identified in urine by GC‐MS on a chiral stationary phase after consumption of 100 mg of 1,8‐cineole. Metabolite screening using 2H3‐1,8‐cineol as the internal standard revealed (+/−)‐α2‐hydroxy‐1,8‐cineole as the predominant metabolite followed by (+/−)‐9‐hydroxy‐1,8‐cineole. Furthermore, the results showed that one enantiomer is always formed preferentially.

A straightforward and general access to α-phthalimido-α′-substituted propan-2-ones

The regioselective ring opening of the commercially available N-(2,3-epoxypropyl)phthalimide with different nucleophiles, to obtain the corresponding phthalimidopropan-2-ols (including a challenging fluorohydrin) followed by the Dess–Martin periodinane oxidation, constitutes a general and widely applicable protocol for the preparation of differently functionalized α-phthalimido-α′-substituted propan-2-ones. The incorporation of the substituent in the α′ position takes place in an early stage of the process, thus furnishing a divergent and valuable approach.

Novel Synthesis of 2‐Amino‐1,4‐benzoquinone‐4‐phenylimides from Anilines via Dess—Martin Periodinane Oxidation.

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Design, Synthesis, and Biological Activity of m-Tyrosine-Based 16- and 17-Membered Macrocyclic Inhibitors of Hepatitis C Virus NS3 Serine Protease

The limited efficacy and considerable side effects of currently available therapies for the treatment of hepatitis C virus (HCV) infection have prompted significant efforts toward the development of safe and effective new therapeutics. The pentapeptide alpha-ketoamides of type 1 were weak HCV inhibitors with a binding constant, Ki, above 5 microM. We envisioned that cyclization of a P2 phenyl side chain to a P3 capping group could enhance binding through an interaction of the resulting macrocycle with the methyl group of Ala156 on the enzyme backbone. The macrocyclic dipeptide moiety would also decrease the peptidic nature of the inhibitors. The synthesis of macrocyclic HCV inhibitors started from m-tyrosine methyl ester. Two consecutive couplings, first, with Boc-cyclohexylglycine and, then, with hept-6-enoic acid, provided compound 6. The alkene was converted to an alcohol via hydroboration. The key macrocyclization of phenol alcohol 7 was achieved through a Mitsunobu reaction. Both 16- and 17-membered macrocycles (8 and 21) were prepared. After hydrolysis, the macrocyclic acids (15 and 22) were coupled to the right-hand tripeptide (14) to afford alpha-hydroxyamides, which upon Dess-Martin periodinane oxidation furnished the desired alpha-ketoamides. Esters, acids, and amides were incorporated at the C-terminal of these peptides. These inhibitors were tested in an HCV protease continuous assay. The binding constants (Ki) indicated that the 16-membered macrocyclic inhibitors (23 and 24) were less potent than the 17-membered analogues (16-19). It was also evident that C-terminal acids (i.e., 17) and amides (18 and 19) (Ki range: 0.16-0.31 microM) were much better inhibitors than tert-butyl esters (16 and 23). The X-ray crystal structure of compound 17 bound to the enzyme revealed that the macrocycle formed a "donut"-shaped ring around the methyl group of Ala156. P2' phenyl and P1 propyl groups wrapped around the Lys136 side chain, forming a "C"-shaped clamp. The 17-membered macrocyclic inhibitors 17-19 were significantly more potent than the acyclic pentapeptide 1.

Rapid Access to Complex Molecular Architectures via o-Azaquinones

A multitude of natural product like molecules such as 2 and 3 can be readily obtained from hydroxyketoamide 1. The versatile 1 is derived, via the intermediate o-azaquinone 4, from the Dess–Martin periodinane oxidation of the corresponding anilide.

Rapid Access to Complex Molecular Architectures viao-Azaquinones

A multitude of natural product like molecules such as 2 and 3 can be readily obtained from hydroxyketoamide 1. The versatile 1 is derived, via the intermediate o-azaquinone 4, from the Dess-Martin periodinane oxidation of the corresponding anilide.

Total Synthesis of Natural PI-091, a New Platelet Aggregation Inhibitor of Microbial Origin.

The total synthesis of a new platelet aggregation-inhibiting gamma-lactam PI-091 (1) gave a 1:1 diastereomeric mixture at the gamma-ketal carbon. The high-yielding aldol reaction of an appropriately protected 1,3,4-trihydroxy-4-methyldecan-2-one 42, prepared from D-glucose, with the kinetically generated enolate of 3-methyl-2-butanone provided 43. The resulting diastereomeric mixture of the aldol adduct 43 was converted to a 2,4-alkylated furan 45 via an intramolecular ketalization followed by dehydration. The addition of a singlet oxygen to the alpha-trimethylsilylated furan 48derived from 45 under photochemical conditions efficiently provided an alpha,gamma-dialkylated gamma-hydroxy gamma-lactone 47. The transformation of methyl ketal 52 prepared from 47 into gamma-hydroxy gamma-lactam 53 was achieved by exposure to liquid ammonia in MeOH. The total synthesis of 1 was achieved from 52 through the Dess-Martin periodinane oxidation of the secondary hydroxy group in the side chain. The present total synthesis revealed that the stereogenic carbon center in the side chain in natural 1 is S.