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 synthesis of oligosaccharides using a palladium-catalyzed glycosylation reaction

The natural all d- and/or unnatural all l-1,4- and 1,6-oligosaccharides were synthesized from furan alcohols using a palladium-catalyzed glycosylation reaction. The 1,4- and 1,6-alpha-manno-disaccharides were achieved in seven total steps starting from chiral furan alcohols. Similarly, 1,4- and 1,6-alpha-manno-trisaccharides were also synthesized in nine total steps. Key to the overall efficiency of this process was the use of highly diastereoselective palladium-catalyzed glycosylations, reductions, and dihydroxylations.     

Simple glycosylation reaction of allyl glycosides

A simple glycosylation strategy employing only allyl glycosides is described. In a one-pot fashion, an allyl glycoside is first isomerized to the reactive 1-prop-en-yl glycoside intermediate, which subsequently undergoes glycosylation with a glycosyl acceptor, promoted by NIS at room temperature.     

A novel palladium-catalyzed arylation-dehydroaromatization reaction: synthesis of 7-aryltetralones

A new one-pot room-temperature palladium-catalyzed synthesis of 7-aryltetralones was discovered. This tandem process includes a palladium-catalyzed gamma-selective arylation of the enone 4 followed by a dehydrogenation-aromatization of the initial cross-coupling product. [reaction: see text]     

Enzyme-catalyzed synthesis of natural and unnatural polysaccharides

Synthesis of natural and unnatural polysaccharide was achieved via “enzymatic polymerization” by utilizing a glycoside hydrolase as catalyst. Particularly, hyaluronan, chondroitin, and their derivatives belonging to glycosaminoglycans have been prepared using sugar oxazoline monomers designed on the basis of the concept “transition-state analogue substrate”. The oxazoline derivatives of N-acetylhyalobiuronate [GlcAβ(1→3)GlcNAc] and N-acetylchondrosine [GlcAβ(1→3)GalNAc], which have the repeating disaccharide structures of hyaluronan and chondroitin, respectively, were successfully polymerized by the catalysis of hyaluronidase, giving rise to synthetic hyaluronan and chondroitin. Their 2-substituted oxazoline derivatives were also polymerized to the corresponding N-acylated hyaluronan and chondroitin derivatives. Furthermore, N-acetylchondrosine oxazoline derivatives sulfated at the C4, the C6, and both the C4 and C6 of the GalNAc unit were catalyzed by hyaluronidase; the monomer sulfated at the C4 was polymerized to chondroitin 4-sulfate with well-defined structure, whereas the other two monomers were exclusively hydrolyzed to the corresponding disaccharides. These different kinds of natural and unnatural polysaccharides having relatively high molecular weights were produced in all cases by the catalysis of hyaluronidase. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5014–5027, 2006     

Proline-catalyzed stereoselective synthesis of natural and unnatural nocardiolactone

A concise diastereo and enantioselective synthesis of natural and unnatural nocardiolactone is accomplished by proline-catalyzed crossed-aldol reaction as the key step.     

De novo asymmetric syntheses of SL0101 and its analogues via a palladium-catalyzed glycosylation

The enantioselective syntheses of naturally occurring kaempferol glycoside SL0101 (1a) and its analogues 1b-e, as well as their enantiomers, have been achieved in 7-10 steps. The routes rely upon a diastereoselective palladium-catalyzed glycosylation, ketone reduction, and dihydroxylation to introduce the rhamno-stereochemistry. The asymmetry of the sugar moiety of these kaempferol glycosides was derived from Noyori reduction of an acylfuran. An acetyl group shift from an axial (C-2) to equatorial position (C-3) under basic conditions was also described. [reaction: see text]     

An approach to the synthesis of dimeric resveratrol natural products via a palladium-catalyzed domino reaction

A route for the rapid assembly of the carbon framework of several resveratrol natural products is presented. A palladium-catalyzed domino reaction of bromostilbene derivative 6 and tolane 7, involving two sequential Heck coupling reactions, provides access to the benzofulvene-based core of various resveratrol-derived natural products. The carbon skeleton of pallidol and its congeners is achieved by a Lewis acid-induced Nazarov-type oxidative cyclization of 9.     

De novo asymmetric synthesis of homoadenosine via a palladium-catalyzed N-glycosylation

[reaction: see text] A highly stereoselective synthesis of l-2-deoxy-beta-ribo-hexopyranosyl nucleosides from 6-chloropurine and Boc-protected pyranone has been developed. Our approach relies on the iterative application of a palladium-catalyzed N-glycosylation, diastereoselective reduction, and reductive 1,3-transposition. This strategy is amenable to prepare various natural and unnatural hexopyranosyl nucleosides analogues.     

Total synthesis of Ciliatamides A-C: stereochemical revision and the natural product-guided synthesis of unnatural analogs

The first total synthesis of Ciliatamides A-C was completed, leading to a revision of the reported stereochemistry from (S,S) to the (R,R) enantiomers. Due to the expedited route, a library of over 50 unnatural ciliatamide analogs was also prepared.     

2-Deoxy-disaccharide approach to natural and unnatural glycosphingolipids synthesis

2-Deoxy-disaccharides were easily converted into glycosylphytosphingosines, as new and efficient precursors of natural and unnatural glycosphingolipids.     

General strategy for the synthesis of natural and unnatural dialkylmaleic anhydrides

Starting from alkylidenesuccinimides, a wide range of dialkylmaleic anhydrides have been synthesized via the generation of a carbanion on a succinimide unit and its condensation with various alkyl halides as the key reaction.     

A de novo synthesis of 2,6-dideoxy-C-aryl glycosides based on ring closing metathesis and diastereoselective epoxide cleavage/anomerization reactions

[formula: see text] This paper describes a synthesis of enantiomerically pure 2,6-dideoxy-C-aryl glycosides, starting from non-carbohydrate precursors. The synthesis starts from homoallylic alcohols (obtained in enantiomerically pure form by enzymatic resolution), which are elaborated to dihydropyrans using ring closing metathesis as the key step. Epoxidation and epoxide cleavage complete the synthesis. The stereochemical outcome of the sequence depends on the conditions of the epoxide cleavage reaction.     

A stereoselective synthesis of digitoxin and digitoxigen mono- and bisdigitoxoside from digitoxigenin via a palladium-catalyzed glycosylation

A convergent and stereocontrolled route to trisaccharide natural product digitoxin has been developed. The route is amenable to the preparation of both the digitoxigen mono- and bisdigitoxoside. This route featured the iterative application of the palladium-catalyzed glycosylation reaction, reductive 1,3-transposition, diastereoselective dihydroxylation, and regioselective protection. The natural product digitoxin was fashioned in 15 steps starting from digitoxigenin 2 and pyranone 8a or 18 steps from achiral acylfuran.     

Total synthesis of phorboxazole A via de novo oxazole formation: convergent total synthesis

The phorboxazoles are mixed non-ribosomal peptide synthase/polyketide synthase biosynthetic products that embody polyketide domains joined via two serine-derived oxazole moieties. Total syntheses of phorboxazole A and analogues have been developed that rely upon the convergent coupling of three fragments via biomimetically inspired de novo oxazole formation. First, the macrolide-containing domain of phorboxazole A was assembled from C3-C17 and C18-C30 building blocks via formation of the C16-C18 oxazole, followed by macrolide ring closure involving an intramolecular Still-Genarri olefination at C2-C3. Alternatively, a ring-closing metathesis process was optimized to deliver the natural product's (2Z)-acrylate with remarkable geometrical selectivity. The C31-C46 side-chain domain was then appended to the macrolide by a second serine amide-derived oxazole assembly. Minimal deprotection then afforded phorboxazole A. This generally effective strategy was then dramatically abbreviated by employing a total synthesis approach wherein both of the natural product's oxazole moieties were installed simultaneously. A key bis-amide precursor to the bis-oxazole was formed in a chemoselective one-pot, bis-amidation sequence without the use of amino or carboxyl protecting groups. Thereafter, both oxazoles were formed from the key C18 and C31 bis-N-(1-hydroxyalkan-2-yl)amide in a simultaneous fashion, involving oxidation-cyclodehydrations. This synthetic strategy provides a total synthesis of phorboxazole A in 18% yield over nine steps from C3-C17 and C18-C30 synthetic fragments. It illustrates the utility of a synthetic design to form a mixed non-ribosomal peptide synthase/polyketide synthase biosynthetic product based upon biomimetic oxazole formation initiated by amide bond formation to join synthetic building blocks.     

An expeditious synthesis of natural and unnatural disubstituted maleic anhydrides

A facile entry to the synthesis of natural and unnatural substituted maleic anhydrides based on the Barton radical decarboxylation is described. The radicals, generated by the photolysis of N-hydroxy-2-thiopyridone esters derived from succinic and alkyl acids reacted, respectively, with electron deficient olefin phenyl maleimide by a consecutive two-step radical addition, afforded the corresponding disubstituted maleic anhydrides 1a-f.     

Chiral economic total synthesis of natural and unnatural prostaglandins]

Using a meso-compound which is asymmetrically substituted with a chiral moiety as an intermediate, prostaglandins have been synthesized. Since the undesired enantiomer is readily recycled, this approach leads to a synthesis with high chiral efficiency. In addition it is possible to prepare both enantiomeric configurations of prostaglandins by simply altering the sequence of reactions. This concept should be generally useful in the synthesis of optically active molecules.     

A de novo Diels-Alder strategy toward the novel pentacyclic natural product fluostatin C: a concise synthesis of 6-deoxyfluostatin C

A conceptually new Diels-Alder approach, involving a diene moiety grafted on a preformed epoxyquinone platform and a 4-hydroxy-indenone as the dienophile, delivers the pentacyclic framework of fluostatin C in one key step.