De Novo Asymmetric Synthesis Research Articles

Progress toward the De Novo Asymmetric Synthesis of Euphanes.

Progress toward an asymmetric synthesis of euphanes is described. A C14-desmethyl euphane system possessing five differentially substituted and electronically distinct alkenes has been prepared. The route employed is based on sequential metallacycle-mediated annulative cross-coupling, double asymmetric Brønsted acid mediated intramolecular Friedel-Crafts alkylation, and an oxidative rearrangement to establish the requisite C10 quaternary center. These studies have also led to the discovery of a novel euphane-based modulator of the Liver X Receptor.

De novo asymmetric synthesis of the mezzettiaside family of natural products via the iterative use of a dual B-/Pd-catalyzed glycosylation.

The first synthesis of any and all members of the mezzettiaside family of natural products has been achieved. The reported synthesis features the iterative use of the Taylor catalyst in a dual nucleophilic boron/electrophilic palladium catalyzed regioselective glycosylation. In addition, the de novo approach utilizes atomless protecting groups and the minimal use of protecting groups (2 chloroacetates for the synthesis of 10 natural products). These divergent syntheses occurred in a range of 13 to 22 longest linear steps and required only 41 total steps to prepare the entire family of mezzettiasides.

De Novo Asymmetric Synthesis of an α-6-Deoxyaltropyranoside as Well as its 2-/3-Deoxy and 2,3-Dideoxy Congeners

A highly divergent de novo asymmetric synthesis of benzyl alpha-6-deoxyaltropyranoside, benzyl alpha-ascarylopyranoside, benzyl alpha-amicetopyranoside, and benzyl alpha-digitoxopyranoside has been achieved via a common pyranone intermediate. The routes rely upon a palladium(0)-catalyzed glycosylation reaction and corresponding post-glycosylation transformations. The control of the absolute and relative stereochemical configuration came from a Noyori reduction of 2-acylfuran and subsequent diastereoselective introduction of other stereogenic centers.

De Novo Asymmetric Synthesis of Cladospolide B−D: Structural Reassignment of Cladospolide D via the Synthesis of its Enantiomer

The enantioselective synthesis of cladospolide B, C, and (ent)-cladospolide D has been achieved in 11-15 steps from 1-nonyne. The route relies upon an alkyne zipper reaction to relay an ynone and dienoate functional groups across a nine carbon fragment, which enables a highly enantioselective Noyori ynone reduction and a diastereo- and regioselective Sharpless dihydroxylation of a dienoate. In addition to being a flexible approach to three members of the cladospolide natural products, this route for the first time correctly established the structure for cladospolide D.

De Novo Asymmetric Synthesis and Biological Evaluation of the Trisaccharide Portion of PI-080 and Vineomycin B2

A highly enantio- and diastereoselective synthesis of an alpha-L-aculose, alpha-L-rhodinose, and beta-D-olivose trisaccharide is described. The key transformations include the palladium-catalyzed glycosylation, Myers' reductive rearrangement, diastereoselective dihydroxylation, and regioselective Mitsunobu inversion. Significant apoptotic antitumor activity was found for this trisaccharide, which has implication for vineomycin B2 and PI-080 structure-activity relationship.

De Novo Asymmetric Synthesis of the Anthrax Tetrasaccharide by a Palladium‐Catalyzed Glycosylation Reaction.

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De Novo Asymmetric Synthesis of the Anthrax Tetrasaccharide by a Palladium‐Catalyzed Glycosylation Reaction

De Novo Asymmetric Synthesis of the Anthrax Tetrasaccharide by a Palladium‐Catalyzed Glycosylation Reaction

De Novo Asymmetric Synthesis of the Anthrax Tetrasaccharide by a Palladium‐Catalyzed Glycosylation Reaction

Freie Giftwahl: In der asymmetrischen De-novo-Synthese des Anthraxtetrasaccharids 1 (25 Stufen ausgehend von Acetylfuran) wurden die Absolutkonfigurationen dreier L-Zucker und des D-Zuckers durch die Noyori-Reduktion von Acetylfuran mit dem S,S- bzw. R,R-Reagens gesteuert. Die Konfiguration der letzten Kohlenhydrateinheit wurde durch eine hoch diastereoselektive palladiumkatalysierte Glycosylierung und anschließende Umwandlungen festgelegt.

De Novo Asymmetric Synthesis of Milbemycin β3 via an Iterative Asymmetric Hydration Approach

The enantioselective synthesis of the spiroketal/macrolide natural product milbemycin beta3 has been achieved in 22 steps and 2.8% overall yield from an achiral dienoate. The spiroketal ring system was installed by three sequential asymmetric hydrations followed by sprioketalization. Both the absolute and relative stereochemistry of milbemycin beta3 was introduced by two Sharpless asymmetric dihydroxylations, two pi-allylpalladium-catalyzed reductions, and an iridium-catalyzed hydrogen migration/Claisen rearrangement to install the C-12 stereocenter.

De Novo Asymmetric Synthesis of Daumone via a Palladium‐Catalyzed Glycosylation.

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De Novo Asymmetric Synthesis of Anamarine and Its Analogues

[reaction: see text] The enantioselective synthesis of anamarine has been achieved in 21 steps. The route relies on enantio- and regioselective Sharpless dihydroxylation of dienoate ester and zinc borohydride reduction to establish the C-8-C-11 stereochemistry. A diastereoselective Leighton allylation established the desired C-5 stereochemistry. The route has also been used to prepare two diastereoisomers of anamarine in 14 steps.

De Novo Asymmetric Synthesis of Daumone via a Palladium-Catalyzed Glycosylation

The enantioselective syntheses of daumone and two analogues have been achieved in seven to eight steps. This route relies upon a diasteroselective palladium-catalyzed glycosylation reaction for the formation of the anomeric bond. The asymmetry of the sugar and aglycone portion of daumone were introduced by Noyori reduction of an acylfuran and a propargyl ketone. A highly diastereoselective epoxidation and reductive ring opening established the desired C-2 and C-4 stereochemistry of daumone. [reaction: see text]

De Novo Asymmetric Synthesis of Protected 5-O-Carbamoylpolyoxamic Acid

De Novo Asymmetric Synthesis of Protected 5-O-Carbamoylpolyoxamic Acid