Dess-Martin Oxidation Research Articles

Synthetic studies on fusicoccin A: Enantioselective synthesis of the C-ring fragment

The enantioselective synthesis of the C-ring fragment of fusicoccin A is described. The TBS ether of hydroxyketone prepared by baker’s yeast reduction was converted to the α-ethylidene ketone by aldol condensation with propionaldehyde, followed by Michael reaction with divinylcopper reagent and conversion to enol triflate to afford a single diastereomer. X-ray crystallographic analysis of the crystalline derivative of the single diastereomer showed that the asymmetric carbon formed by the Michael reaction was consistent with the configuration of the C15 asymmetric carbon of fusicoccin A. The vinyl group of the enol triflate was converted to a hydroxymethyl group by selective dihydroxylation with a bulky ligand, oxidative cleavage of the resultant 1,2-diol with lead tetraacetate, and DIBAL-H reduction. The hydroxymethyl group was subsequently converted to TBS ether, followed by the hydrogenolysis of the benzyl group and Dess–Martin oxidation, accomplishing the enantioselective synthesis of the desired C-ring fragment of fusicoccin A.

Dess-Martin oxidation of hydroxypropyl and hydroxyethyl cellulose, and exploration of their polysaccharide/polypeptide hydrogels

Oxidation of polysaccharides can provide biomaterials with aldehyde and ketone functional groups, which are particularly useful in biomedical applications, like drug delivery, tissue adhesion and hydrogel preparation. However, despite their potential, only a few such methods have been reported, and achieving selective, quantitative oxidation of polysaccharides remains challenging. Herein we report utilization of a mild oxidant, Dess-Martin periodinane, for the chemoselective oxidation of hydroxypropyl cellulose (HPC) and hydroxyethyl cellulose (HEC). Our findings reveal that the oxidation of HPC is fast, efficient and achieves near-quantitative conversion. Moreover, both Ox-HPC and Ox-HEC exhibit low cell toxicity, and readily form hydrogels by reaction with a polypeptide comprising amino acids with amine-containing a-substituents, α-poly-l-lysine. The peptide/polysaccharide hydrogels display self-healing properties, injectability, and antimicrobial activity, making them highly attractive for biomedical applications including in wound dressings.

Synthesis of (±)-Ingenol

Key words (±)-ingenol - De Mayo reaction - Corey–Posner–Whitesides–House reaction - Upjohn Dihydroxylation - Dess–Martin oxidation - Luche reduction

Curious Case of Cobaltocenium Carbaldehyde.

Cobaltocenium carbaldehyde (formylcobaltocenium) hexafluoridophosphate, a long sought-after functionalized cobaltocenium salt, is accessible from cobaltocenium carboxylic acid by a three-step synthetic sequence involving (i) chlorination to the acid chloride, (ii) copper-borohydride reduction to the hydroxymethyl derivative, and (iii) Dess-Martin oxidation to the title compound. Due to the strongly electron-withdrawing cationic cobaltocenium moiety, no standard aldehyde reactivity is observed. Instead, nucleophilic addition followed by haloform-type cleavage prevails, thereby ruling out common useful aldehyde derivatization. One-electron reduction of cobaltocenium carbaldehyde hexafluoridophosphate affords the deep-blue, isolable cobaltocene carbaldehyde 19-valence-electron radical whose spin density is located fully at cobalt and not at the formyl carbon atom. 1H/13C NMR, IR, EPR spectroscopy, high-resolution mass spectrometry, cyclic voltammetry, single crystal structure analysis (XRD), and density functional theory are applied to characterize these unusual formyl-cobaltocenium/cobaltocene compounds.

Application of The Dess-Martin Oxidation in Total Synthesis of Natural Products.

Dess-Martin periodinane (DMP), a commercially available chemical, is frequently utilized as a mild oxidative agent for the selective oxidation of primary and secondary alcohols to their corresponding aldehydes and ketones, respectively. DMP shows several merits over other common oxidative agents such as chromiumand DMSO-based oxidants; thus, it is habitually employed in the total synthesis of natural products. In this review, we try to underscore the applications of DMP as an effective oxidant in an appropriate step (steps) in the multi-step total synthesis of natural products.

A Convenient Synthesis of (16S,20S)-3β-hydroxy-5α-pregnane-20,16-carbolactam and its N-alkyl Derivatives.

A concise synthesis of (16S,20S)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route consisted of the lactone ring-opening with aminoalane reagent followed by PDC or Dess-Martin oxidation. The oxo-amide obtained was subjected to cyclization with Et3SiH/TFA or Et3SiH/Bi(TfO)3. Alternately, the lactone was converted first to the oxo-acid, which was then subjected to the microwave-assisted reductive amination. N-Alkyl derivatives were also obtained in a similar way.

Enantioselective Synthesis of the Proposed Structure of Santinol D

In connection with structural verification of santinol D, a unique tricylglycerol isolated from Helichrysum italicum subsp. microphyllum, four possible isomers of its C‐2'''and C‐4''' centers were synthesized. The two enolizable chiral centers were installed with pre‐defined absolute configurations using Evans alkylation and aldol condensation, respectively. The extra chiral center introduced in the aldol condensation was removed by Dess–Martin oxidation to convert the adjacent methine group into the highly enolizable subunit of an α‐alkyl‐β‐keto ester at the end of the synthesis. The synthetic isomers provided unequivocal physical and NMR data for every single enantiomer and thus provided the information required for the configurational assignment of this natural product. With the aid of a model compound, the racemization of such species was examined polarimetrically under several sets of typical conditions and the rates were also calculated from the corresponding kinetics data.

Synthesis directed towards trans-clerodanes employing an exo-selective Diels–Alder reaction as a key-step

A potential intermediate in the synthesis of several trans-clerodane natural products has been constructed employing a Diels–Alder reaction as a key-step. Two epimeric exo-adducts were formed in a 4:3 ratio in an EtAlCl2-mediated cycloaddition of O-silylated 2-vinylcyclohex-2-enol and N-tigloylisoxazolidinone. Both isomers were converted to the trans-clerodane intermediate in four steps; reductive removal of the oxazolidinone, followed by O-benzylation, removal of the silyl protecting group, and, finally, a Dess–Martin oxidation of the deprotected alcohol to the corresponding ketone. It was possible to transform both isomers from the cycloaddition into the final target, but the major isomer was converted at greater yields. An interesting discovery made during the work was that the desilylation demanded significantly different conditions depending on which isomer was deprotected. The fact that the cycloaddition not only resulted in an excellent exo-selectivity, but also that the alkene to a large extent approached from the least hindered side, opens the possibility for enantioselective synthesis of the target compound from (R) or (S) diene starting materials in the future.

Scopuquinolone B, a new monoterpenoid dihydroquinolin-2(1H)-one isolated from the coral-derived Scopulariopsis sp. fungus

Further chemical investigation of the secondary metabolites of the fungus Scopulariopsis sp. led to the discovery of a new alkaloid, scopuquinolone B (1). The structure of compound 1 was elucidated by extensive NMR spectroscopic data, CD spectrum and analysis of its Dess-Martin oxidation derivative. Compound 1 was evaluated for antilarval settlement activity of barnacle Balanus amphitrite and showed promising antifouling activity with an EC50 value of 0.103 μM and a high therapeutic ratio of 222.

Synthesis and Plant Growth Regulating Activities ofiso-Abscisic Acid

The iso-abscisic acid (iso-ABA) analogs 11, 12, 13 and 14 were synthesized via regioselective addition of ace- tylides to enediones, selective reduction, Dess-Martin oxidation and Lindgren oxidation. The racemic mixtures 11 were re- solved by chiral HPLC. These iso-ABA analogs and ABA were tested for their inhibitory activity in four bioassays. (+)-iso-ABA 11 exhibited high ABA-like activity, including the ability to effectively inhibit seed germination and seedling growth. The analogs 12, 13, 14 were also prepared and biological activities were investigated. Comparison of four bioassays, the iso-abscisic acid analogs had better activity in lettuce seed germination.

A Novel Method for the Synthesis of Latanoprost

Latanoprost is a kind of PGF2α analogues, which is now one of the first-choice drugs in the clinic for open angle glaucoma and ocular hypertension. However, the previous synthetic methods have problems of long steps, low yield and diffi- cult separation of isomeric impurities. Herein, we report a novel method for the synthesis of latanoprost in ten steps. Benzoyl Corey lactone as starting material was oxidized to form corresponding aldehyde by Dess-Martin oxidation. The ω side chain was bonded by improving Horner-Wadsworth-Emmons reaction with dimethyl(2-oxo-4-phenylbutyl)phosphonate and lithium chloride, and reduced with (-)-diisopinocampheyl chloroborane at -30 ℃ because of its greater selectivity towards the production of desired S-isomer (95%). The deprotection step wherein the protecting group of benzoyl on the hydroxyl group of the cyclopentane ring was removed, was preferably carried out by potassium carbonate in methanol. The hydrogenation of double bond in ω side chain was carried out by using 5% palladium-carbon as catalyst. The tetrahydropyranyl (THP) group was used for the protection of the diol with p-toluenesulfonic acid as catalyst. Latanoprost lactol was obtained by reducing the lactone with diisobutylaluminum hydride (DIBAL) at -78 ℃. α side chain of latanoprost was bonded by Wittig reaction with 4-carboxybutyl triphenylphosphoium bromide and NaHMDS forming phosphorus ylide. The carboxylic acid was alky- lated with isopropyl iodide in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU), and then removed the THP protect- ing groups with pyridinium 4-toluenesulfonate (PPTS). Latanoprost was separated from two isomers of 15(S)-latanoprost and 5,6-trans-latanoprost after purification by normal-phase high performance liquid chromatography. Thus latanoprost was ob- tained with high purity of 99.91% and high overall yield of 19.2%, and the structure was characterized by 1 H NMR, 13 C NMR, IR and HRMS. Compared with the previous routes, the current synthesis is shorter, more practical, and more suitable for large-scale preparation.

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A.

A concise enantioselective synthesis of the advanced intermediate 5 for the synthesis of pumiliotoxins (Gallagher’s intermediate) is described. The synthesis started from the regio- and trans-diastereoselective (dr = 98:2) reductive 3-butenylation of (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14. After O-desilylation and Dess–Martin oxidation, the resulting keto-lactam 10 was subjected to a highly trans-stereoselective addition of the methylmagnesium iodide to give carbinol 11 as sole diastereomer. An efficient ring closure procedure consisting of ozonolysis and reductive dehydroxylation provided the indolizidine derivative 5, which completed the formal enantioselective total synthesis of pumiliotoxins 251D and 237A.

Enabling Access to Diverse Bioactive Molecules Through Enyne Metathesis Concepts

This paper surveys recent advances in valorization of transition-metal-catalyzed enyne metathesis as key events in the total synthesis of naturally occurring compounds of biological and medicinal importance. Special attention is devoted to methodologies based on dienyne ring-closing metathesis (RCM) applied in tandem and sequential processes, on relay ring-closing metathesis (RRCM), ringrearrangement metathesis (RRM), enyne cross-metathesis (CM) and enyne skeletal bond reorganization, all proceeding under metalcarbenes (Ru or Mo alkylidenes) or metal-salts (Pd or Pt) catalysis. The high potential of these procedures in constructing versatile scaffolds as essential structural cores of a diversity of bioactive natural products is highlighted. Inventive functionalizations by nonmetathesis transformations intervening in the total synthesis of the targeted natural compounds, prior to (Michael addition, Wittig olefination, allylation etc.) or after (Diels-Alder cycloaddion, Heck and Suzuki-Miyaura reactions, Dess-Martin oxidation, dihydroxylation, epoxidation etc.) the pivotal metathesis step have also been included.

Unexpected N-glycosidation reaction of glycals with 1-amino-anthracene: structure revision and application to the synthesis of new analogues of marmycin A

An unexpected N-glycosidation reaction of anthracen-1-amine with glycals was identified, and its use in the synthesis of C1' N-linked analogues of natural product marmycin A was explored. The structures of all these products were determined by 1D and 2D NMR, CD spectra, and X-ray crystal analysis. These products were then subjected to Friedel-Crafts acylation, Dess-Martin oxidation and nucleophilic addition leading to novel natural product analogues bearing a quaternary carbon center.

A Versatile Approach to Alcohol, Aldehyde, Ketone and Amine Derivatives Starting from β-Allyl C-Glycosides of d-Ribofuranose and 2-Deoxy-d-ribofuranose

An efficient preparative procedure is described, leading from β-allyl C-glycosides of d-ribofuranose to alcohols by a hydroboration-oxidation procedure. The corresponding aldehydes were obtained by Swern or Dess-Martin oxidation. Alternatively, two of the alcohols were mesylated to gain access to azides and amines. Treatment of the aldehydes with ethynylmagnesium bromide or phenylethynyllithium and consecutive oxidation of the diastereomeric­ alcohols provided the acetylenic ketones in good to excellent yields. The obtained derivatives serve as important intermediates for the synthesis of various heterocyclic systems.

A Straightforward Approach towards Functionalized γ-Hydroxy and Heterocyclic Amino Acids

Regioselective ring opening of epoxides by chelated enolates in combination with Dess-Martin oxidation provides a straightforward approach towards γ-oxo amino acids, which are ideal substrates for carbonyl additions and the synthesis of heterocycles.

Synthesis of allylic trifluoromethyl ketones and their activity as inhibitors of the sex pheromone of the leopard moth, Zeuzera pyrina L. (Lepidoptera: Cossidae)

Trifluoromethyl ketones (TFMKs), structurally related to the pheromones, are good inhibitors of pheromone communication in insects. To determine their activity on Zeuzera pyrina L. (Lepidoptera: Cossidae), a polyphagous pest, the authors have prepared two diunsaturated TFMK analogues of the major (3) and the minor (4) pheromone components, and two monounsaturated ones (5, 6). Their biological activity in electroantennogram (EAG), wind tunnel and field tests is presented. The synthetic strategy to obtain the allylic TFMKs 3 and 5 is based on the reactions of diene 10 and 1-octadecene with trifluoroacetaldehyde ethyl hemiacetal, followed by Dess-Martin oxidation of the resulting homoallylic trifluoromethyl alcohols. In EAG, topical application of analogues 3 and 4 on male antennae significantly reduced the pheromone response. In the wind tunnel, compound 4 reduced the number of contacts with the pheromone source. In the field, traps baited with mixtures of pheromone and inhibitors captured significantly fewer males than the pheromone alone. An efficient synthesis of allylic TFMKs is reported, with good overall yield, regiospecificity and diastereoselectivity. These compounds are good inhibitors of the pheromone in electrophysiology, wind tunnel and field tests. The results show the importance of two unsaturations at positions 2 and 13 of the trifluoroacyl group in the structure of the analogues, the latter being critical for inhibitory activity.

ChemInform Abstract: Acceleration of the Dess-Martin Oxidation by Water.

The Dess-Martin periodinane (DMP), l,l,l-triacetoxy-l,l-dihydro-l,2-benziodoxol-3(LH)-one (2),l is one of the mildest and most convenient reagents available for oxidation of alcohols (Figure 1). DMP enjoys increasing use despite suggestion that its behavior can be capricious.2 Recently, Ireland has addressed a problem of inconsistency in DMP batch quality by offering an improved procedure for synthesizing the reagenta2 Important as it is to have a reliable method of preparing pure DMP, we suspect that many D-M (Dess-Martin) oxidations in the literature have been effected not by DMP, but by an impurity commonly present in DMP samples. In our own laboratory, a crucial D-M oxidation in the total synthesis of rapamycin3 proceeded consistently only with a single 2-year old batch of the reagent, material that was largely insoluble in CDC13 and that exhibited a complex proton NMR spectrum. Several other samples of DMP, including relatively pure reagent prepared according to the Ireland method,2 failed to perform the desired transformation. Questions about the composition of the effective sample motivated the present Dess-Martin periodinane study. In attempts to obtain the impurities present in the effective DMP reagent, we explored Dess and Martin's preparation of the oxidant. However, pure, crystalline DMP was reproducibly obtained using their procedure by adhering to the following details: (1) In order to permit greater ease of stirring during oxidation of iodobenzoic acid, the initially viscous reaction mixture was more dilute than in the D-M preparation, which may ensure that oxidation proceeds to ~ompletion.~ (2) Iodinane oxide 1 was heated at 85 C in Ac20 and AcOH at least 1 h beyond the time that dissolution was complete. (3) After acetylation, the mixture was allowed to stand for 1-2 days to permit crystallization of DMP.5 (4) During isolation of the product, exposure to atmosphere was strictly avoided. The resulting DMP was crystalline and completely soluble in CH2Clz and CDC13. The reagent contained a small amount of AcOH, but otherwise its NMR spectra showed no significant (>3%) extraneous peaks. When pure DMP prepared as above was used under inert conditions (flame-dried glassware, dry solvents,

ChemInform Abstract: Synthesis of L-3′-Hydroxymethylribonucleosides.

The target compounds were synthesized via the key intermediate carbohydrate 8, which was synthesized by first selectively protecting the 1'- and 2'-hydroxyl groups followed by selective tosylation of the 5'-hydroxyl group to obtain compound 3. The tosyl moiety was then replaced by a benzyl either to obtain 4. Compound 4 underwent Dess-Martin oxidation to afford the ketone 5. Compound 5 was subjected to Wittig olefination to afford the alkene 6 followed by regioselective hydroboration to obtain 7. Compound 7 was fully acetylated using acetic acid, acetic anhydride and sulfuric acid to obtain the key intermediate 8.

Thieme Chemistry Journal Awardees - Where Are They Now? Stereoselective Synthesis of Z-Configured α,β-Unsaturated Macrocyclic Lactones and Diolides by Intramolecular Julia-Kocienski Olefination

ω-Sulfonyl aldehydes derived from the esterification of (benzothiazol-2-ylsultonyl)acetic acid with either ω-alkenols or α,ω-diols, followed by ozonolysis or Dess―Martin oxidation as appropriate, underwent intramolecular Julia―Kocienski olefination when treated with DBU. Macrocyclic α,β-unsaturated lactones of between 12- and 19-membered ring sizes were formed successfully using this tactic (24―44% yield, Z/E ≥ 3.5:1); however, diolides were selectively produced from precursors intended to target seven-to nine-membered-ring lactones (13―70% yield, ZZ/ZE ≥ 2:1).