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.     

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.     

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.     

Divergent total synthesis of the natural antimalarial marinoquinolines A, B, C, E and unnatural analogues

A new synthetic route to marinoquinolines was developed, allowing the synthesis of several structurally related compounds from a common key intermediate. Four natural marinoquinolines (A, B, C and E) and nine unnatural new analogues were prepared by this strategy, which features a Heck-Matsuda reaction in pure water and the Pictet-Spengler reaction as key steps.     

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.     

Asymmetric total synthesis of natural (-)-and unnatural (+)-steganacin : Determination of the absolute configuration of natural antitumor steganacin

A virtually complete asymmetric control in the synthesis of 2,3-disubstituted butan-4-olide (10) was demonstrated by employing the butenolide (12) as the chiral acceptor for the conjugate 1,4-addition. Highly efficient asymmetric total synthesis of natural (-)- and unnatural (+)-steganacin was accomplished. The absolute stereostructure of natural antitumor steganain was determined to be 1.     

Total synthesis of natural and unnatural lamellarins with saturated and unsaturated D-rings

Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and alpha-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography.     

Design and total synthesis of unnatural analogues of the sub-nanomolar SERCA inhibitor thapsigargin

Thapsigargin is a densely oxygenated guaianolide which displays potent sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) binding affinities. The total syntheses of designed unnatural analogues of this important natural product are described. This article constitutes the chemical synthesis behind an ongoing project. Rational modifications have been made to the lactone region of thapsigargin in order to obtain derivatives for future structure-activity relationship studies.     

Chiral,biomimetic total synthesis of (−)-aplysistatin

The marine antineoplastic agent aplysistatin ($\text{6}$) has been prepared enantiospecifically. The key step is the biomimetic cyclization of (2R, 3R)-2-homogeranyl-3,4-dihydroxybutanoic acid 1 4 lactone ($\text{3}$)_with 2,4,4,6-tetrabromocyclohexa-2,5-dienone in nitromethane.     

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.     

A palladium-catalyzed glycosylation reaction: the de novo synthesis of natural and unnatural glycosides

A highly stereoselective and sterospecific palladium-catalyzed glycosylation reaction of a variety of alcohols is reported. The reaction selectively converts alpha-2-substituted 6-carboxy-2H-pyran-3(6H)-ones into alpha-2-substituted 6-alkoxy-2H-pyran-3(6H)-ones with complete retention of configuration and similarly converts the pyranones with beta-carboxy groups into pyranones with beta-alkoxy groups. The reaction works equally well with both amino acid- and carbohydrate-based alcohols. To demonstrate the utility of this process for carbohydrate chemistry several of the products were selectively converted into alpha-manno-pyranosides in two additional steps. Because the 2-substituted 6-carboxy-2H-pyran-3(6H)-ones are prepared by asymmetric synthesis, this reaction can be used for the preparation of either d- or l-pyranones.     

Total synthesis of racemic,natural (+) and unnatural (−) scorzocreticin

The first total synthesis of racemic scorzocreticin and its pure enantiomers is described from readily available 3,5-dihydroxybenzoic acid. The key steps include Wittig olefination, asymmetric Me-CBS (Corey–Bakshi–Shibata) oxazaborolidine reduction, and improved Pd-catalyzed intramolecular lactonization reactions. Both the (S)-natural and (R)-unnatural enantiomers of scorzocreticin have been synthesized in excellent enantioselectivities (>99% and 99% ee, respectively). In addition, 1,10-phenanthroline, a bidentate N-ligand was employed in palladium-catalyzed intramolecular carbonylation/lactonization reaction for the construction of 3,4-dihydroisocoumarin ring.     

Chiral and stereoselective total synthesis of (−)-deoxoprosopinine and (−)-deoxoprosophylline

(?)-Deoxoprosopinine and (?)-deoxoprosophylline were synthesized starting from $\text{L}$-serine by a route involving the intramolecular aminomercuration of a chiral ?,ζ-unsaturated amine.     

Synthetic approaches and total synthesis of natural zoapatanol

[structure: see text] The total synthesis of (+)-zoapatanol utilizing an intramolecular Horner-Wadsworth-Emmons olefination and an enantioselective Sharpless dihydroxylation as the key steps has been achieved. An advanced oxepene intermediate has been obtained by applying a ring-closing metathesis to an unsaturated enol ether.     

Chemoenzymatic total synthesis of cryptocaryalactone natural products

A new chemoenzymatic route for the preparation of cryptocaryalactones natural products using a kinetic resolution process as the key step is described. Novozyme-435 catalyzed hydrolysis of the prochiral (±)-monoester 7 afforded the precursors of cryptocaryalactones with high enantiomeric excess and excellent yields. The compounds (4S,6S)-7 and (4R,6R)-7 were converted to (+)-(6R,2′S)-cryptocaryalactone (1) and (?)-(6S,2′R)-cryptocaryalactone (2), respectively by employing Wittig-olefination, lactonization and acylation reactions.     

Enantioselective total synthesis of a natural iridoid

The first total synthesis of 6-hydroxy-7-(hydroxymethyl)-4-methylenehexahydrocyclopenta[c]pyran-1(3H)-one has been accomplished. A key feature of the synthesis includes facile construction of the bicyclic lactone intermediate via intramolecular Pd(0)-catalyzed allylic alkylation and the efficient transformation of this intermediate into the iridoid skeleton employing silicon tethered radical cyclization.     

The first total synthesis of natural grenadamide

A concise, high yielding route to the naturally occurring enantiomer of grenadamide utilizing a 3,6-disubstituted 1,2-dioxine starting material is presented. The route allows for ease in synthesizing grenadamide derivatives varying at cyclopropyl carbons 2 and 3, with access to both enantiomers. Evidence for phosphorus-assisted deprotonation of 1,2-dioxines is also discussed.