Asymmetric synthesis of (R)-(+)-etomoxir via enzymatic resolution

An asymmetric synthesis of (R)-(+)-etomoxir 3, employing enzymatic resolution of ethyl 2-alkyl-2,3-dihydroxypropionate using Amano AK via transacylation is reported.     

Stereoselective total synthesis of (+)-cardiobutanolide and (+)-3-epi-cardiobutanolide from diacetone d-glucose

A chiron approach starting with 3-O-benzyl-1,2-O-isopropylidene-α-d-xylo-pentodialdo-1,4-furanose utilizing a Grignard reaction, Mitsunobu stereoinversion, ethyl diazoacetate addition, and selective reduction of the ketone is employed as a key step for the total synthesis of (+)-cardiobutanolide described; a similar strategy is also reported for the first total synthesis of (+)-3-epi-cardiobutanolide.     

A novel concise total synthesis of (+)-lentiginosine

A total synthesis of (+)-lentiginosine was achieved by using ethyl 3-(pyridin-2-yl)acrylate N-oxide as the starting material and an improved Sharpless asymmetric dihydroxylation as the key step.     

A concise enantioselective synthesis of the fungal metabolite (+)-decarestrictine L

A stereoselective 10-step synthesis of the fungal metabolite (+)-decarestrictine L from commercially available ethyl (R)-3-hydroxybutyrate is described in which tandem oxonium ylide formation and rearrangement is used to construct the tetrahydropyranyl core of the natural product.     

Asymmetric syntheses of (+)-negamycin, (+)-3-epi-negamycin and sperabillin C via lithium amide conjugate addition

The chemo- and enantioselective reduction of ethyl 4-chloroacetoacetate and the diastereoselective conjugate addition of enantiopure lithium N-benzyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester have been used as the key steps in the total asymmetric syntheses of (+)-negamycin (in 13 steps and 24% overall yield), (+)-3-epi-negamycin (in 13 steps and 10% overall yield) and sperabillin C (in 17 steps and 13% overall yield) from commercially available starting materials.     

Asymmetric synthesis of (+)-trachyspic acid

Aldol reaction of di-tert-butyl 4-(4-methoxybenzyloxy)-2-oxobutanoate with pent-4-enal using (S)-1-(3,5-bis(trifluoromethyl)phenyl)-3-(pyrrolidin-2-ylmethyl)thiourea hydrochloride as a catalyst, followed by Pinnick oxidation and tert-butyl esterification, gave (2S,3S)-di-tert-butyl 2-(2-(4-methoxybenzyloxy)ethyl)-3-allyl-2-hydroxysuccinate in high optical purity (85% ee), from which the total synthesis of (+)-trachyspic acid, a tumor cell heparanase inhibitor, was accomplished.     

Total synthesis of (+)-epiepoformin, (+)-epiepoxydon and (+)-bromoxone employing a useful chiral building block, ethyl (1R,2S)-5,5-ethylenedioxy-2-hydroxycyclohexanecarboxylate

Enantioselective total synthesis of (+)-epiepoformin 1, (+)-epiepoxydon 2 and (+)-bromoxone 3 using a chiral building block, ethyl (1R,2S)-5,5-ethylenedioxy-2-hydroxycyclo- hexanecarboxylate 6, is described. Since the synthesis afforded intermediates 18, 2 and 25, it accomplished a formal synthesis of (−)-theobroxide 19, (−)-phyllostine 22, (+)-herveynone 27 and (−)-asperpentyn 28. The usefulness of 6 for the synthesis of natural epoxycyclohexene derivatives was demonstrated.     

Formal enantioselective synthesis of (+)-vincamine. The first enantioselective route to (+)-3,14-epivincamine and its enantiomer

A formal synthesis of (+)-vincamine (1) from (S)-(+)-2-ethyl-2-(2-methoxycarbonylethyl) cyclopentanone (6a) is described. This intermediate had previously been obtained by our research group in 90% ee through d'Angelo's deracemizing alkylation of the chiral imine 7, easily prepared from (R)-(+)-α-methylbenzylamine and 2-ethyl cyclopentanone with methyl acrylate. A potencial advanced intermediate for the synthesis of (+)-4, an epimer of (+)-1 at positions C-3 and C-14, has also been prepared from 6a.     

A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B

A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-nocardione B is described. The synthesis is completed in six steps in overall yields of 8% for eleutherin and 14% for allo-eleutherin. The synthetic strategy features an efficient combination of the Dötz annulation reaction with a chiral alkyne and an oxa-Pictet Spengler reaction as the keys steps in the stereodivergent synthesis of (+)-eleutherin and (+)-allo-eleutherin. The synthesis of (S)-(+)-2-(2′-hydroxypropyl)-5-methoxy-1,4-naphthoquinone entails the formal synthesis of (+)-nocardione B.     

First catalytic enantioselective synthesis of the cocaine abuse therapeutic agent (S)-(+)-1-(4-{2-[bis(4-fluorophenyl)methoxy]ethyl}piperazin-1-yl)-2-phenyl-2-propanol

(S)-(+)-1-(4-{2-[Bis(4-fluorophenyl)methoxy]ethyl}piperazin-1-yl)-2-phenyl-2-propanol, which is a promising candidate as a cocaine abuse therapeutic agent, is prepared in several steps. The key asymmetric step is the catalytic enantioselective addition of dimethylzinc to either 2-chloro or 2-bromoacetophenone catalyzed by the use of different chiral isoborneolsulfonamide ligands in the presence of titanium tetraisopropoxide. The synthesis of a new isoborneolsulfonamide ligand bearing a trifluromethyl substituent and its use in this addition is also presented.     

Stereoselective total synthesis of (+)-varitriol

Stereoselective total synthesis of (+)-varitriol, an antitumor natural product, was accomplished by two versatile strategies starting from the commercially available d-(−)-ribose and ethyl (S)-lactate. The key steps involved in the synthesis of the target molecule are epoxidation, cyclization, dihydroxylation and Diels-Alder reaction.     

First enantiospecific synthesis of (+)-β-herbertenol

The first enantiospecific synthesis of (+)-β-herbertenol, from naturally occurring R-(+)-citronellal, employing Taber's diazo decomposition protocol as the key step, is described.     

Application of the Cosford cross-coupling protocol for the stereoselective synthesis of (R)-(+)-goniothalamin, (R)-(+)-kavain and (S)-(+)-7,8-dihydrokavain

An efficient and versatile synthetic method has been developed and utilized for the stereoselective synthesis of (R)-(+)-goniothalamin 1, (R)-(+)-kavain 2 and (S)-(+)-7,8-dihydrokavain 3. Application of the Cosford protocol and direct conversion of aldehydes to β-keto-esters are the key steps in our approach.     

A concise synthesis of (+)-goniofufurone, (+)-7-epi-goniofufurone, (+)-crassalactones B and C

The concise and efficient synthesis of (+)-goniofufurone, (+)-7-epi-goniofufurone, (+)-crassalactones B and C were achieved in 6 to 7 steps from the known d-glucono-δ-lactone derivative 9. An acid-mediated cascade cyclization was employed to construct the furanofurone bicyclic framework in one-pot.     

Total synthesis of natural (+)-sesbanimide a and (-)-sesbanimide b

The first total synthesis of natural (+)-sesbanimide A (1) and (-)-sesbanimide B (2), potent antitumor alkaloids isolated from the seeds of the leguminous plant, Sesbania drummondii, has been accomplished starting from D-(+)-xylose. This total synthesis involves efficient construction of the optically active AB-ring system from D-(+)-xylose, introduction of the C₅-unit into the AB-ring system in a form of exo-methylene-γ-lactone, and elaboration of the labile C-ring system at the last stage of the synthesis. The absolute configurations of natural 1 and 2 could be obviously established by our total synthesis.     

Concise asymmetric synthesis of (R)-(+)-tanikolide

A highly stereoselective total synthesis of (R)-(+)-tanikolide, a δ-lactonic marine natural product, was accomplished in seven steps from easily available starting materials with a 51% overall yield. An asymmetric synthesis of an α-hydroxy aldehyde having a stereogenic quaternary center, by the use of (S)-2-(anilinomethyl)pyrrolidine as a chiral auxiliary, was employed in a key step.     

First total synthesis of (+)-crassalactone A

A simple and highly efficient first total synthesis of cytotoxic (+)-crassalactone A starting from (R)-mandelic acid is described. The strategy involves the osmium tetroxide-catalyzed cis-hydroxylation and the stereoselective addition of ethyl lithiopropiolate to a chiral aldehyde intermediate as key steps.     

Studies on annelation of (+)-2-caranone

Summary The Michael reaction of (+)-2-caranone (1) with methyl vinyl ketone, ethyl vinyl ketone or methyl acrylate was utilized for synthesis of corresponding diketones4 and5 and keto ester8. These compounds were subjected to cyclization to obtain the sesquiterpenoid systems.

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Untersuchungen über die Annelierung von (+)-2-Karanon

Zusammenfassung Die Michaelreaktion von (+)-2-Karanon mit Methylvinylketon, Ethylvinylketon oder Methylakrylat wurde zur Synthese der entsprechenden Diketone4 und5 und des Ketoesters8 genutzt. Diese Verbindungen wurden weiterhin einer Zyklisierung unterworfen, um zu Sesquiterpenoidstrukturen zu gelangen.

     

Synthesis of enantiopure bis-isoxazolines from (4R)-(+)-4-acetoxycyclopent-2-enone

(4R)-(+)-4-Acetoxycyclopent-2-enone was used as a starting material in the stereoselective synthesis of enantiopure bis-isoxazolines.     

A stereoconvergent synthesis of (+)-4-demethoxydaunomycin

Sharpless kinetic asymmetric epoxidation on (±)-2-(l-hydroxyethyl)-5,8-dimethoxy-3,4-dihydronaphthalene (8) followed by LAH reduction gave R-2-(S-l-hydroxyethyl)-2hydroxy-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene and the undesired antipode. The former was converted to R-(-)-2-acetyl-2 hydroxy-5,8-dimethoxy-l,2,3,4-tetrahydronapthalen[R-(-)-5],while the latter was epimerized and recycled. R-(-)-5 has been exploited for the synthesis of(+)-4-demethoxydaunomycin