Geissman-Waiss Lactone Research Articles

Asymmetric Synthesis of N,O-Heterobicyclic Octanes and (-)-Geissman-Waiss Lactone.

A short, asymmetric synthesis of tetrahydro-2H-furo[3,2-b]pyrrole derivatives and (−)-Geissman–Waiss lactone starting from meso-cyclohexadiene epoxide is described. Pivotal transformations in the developed synthetic procedure include asymmetric epoxide ring opening to install the requisite 1S,5S stereocenters and oxidative lactonization/lactamization sequences. This route provides a streamlined synthetic pathway toward necine alkaloids.

Synthesis of (+)- and (−)-Geissman-Waiss lactone from chiral sulfonium salts

A novel series of chiral cyclic zwitterionic pyrrolidinone type intermediates was prepared via regioselective 5-exo-trig-ring-closure of the corresponding chiral sulfonium salts. This synthetic strategy allowed the rapid non-racemic synthesis of the Geissman-Waiss lactone in six steps and 35% overall yield.

A chemical synthesis of 11-methoxy mitragynine pseudoindoxyl featuring the interrupted Ugi reaction

A synthesis of 11-methoxy mitragynine pseudoindoxyl, a new member of the mitragynine class of opioid agonists, from a derivative of the Geissman-Waiss lactone is described. An internal attack of an electron-rich aromatic ring on an electrophilic nitrilium ion and a late-stage construction of the functionalized piperidine ring by the method of reductive cyclization are the pivotal transformations; both ring annulations proceed in a highly diastereoselective fashion. The construction of substituted indoxyl frameworks by the interrupted Ugi method offers an attractive alternative to the strategy of oxidatively rearranging indoles.

Extensive substrate profiling of cyclopentadecanone monooxygenase as Baeyer–Villiger biocatalyst reveals novel regiodivergent oxidations

Cyclopentadecanone monooxygenase (CPDMO) is one of the latest additions to the established library of Baeyer-Villiger monooxygenases. Desymmetrizations of substituted cyclobutanones and -hexanones as well as kinetic resolutions of racemic cycloketones are efficiently catalyzed by CPDMO. Moreover the enzyme shows unprecedented preference in regiodivergent oxidations of terpenones and the bicyclic Geissman-Waiss lactone precursor giving access to the optical antipode of retronecine and other pyrrolizidine alkaloids. (C) 2011 Elsevier B.V. All rights reserved.

ChemInform Abstract: The Shortest Synthesis of Optically Active Geissman-Waiss Lactone, a Key Synthetic Intermediate for Necine Bases.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Synthesis of N-Ethoxycarbonylmethyl Geissman-Waiss Lactone: Unusual Epimerization of α,β-Unsaturated γ-Lactone.

N-Ethoxycarbonylmethyl Geissman-Waiss lactone (±)-2) was easily synthesized from bis-lactone (3), and an unexpected epimerization of γ-butenolactone was observed in the process of asymmetric synthesis of 2

A new enantiodivergent synthesis of the Geissman–Waiss lactone

Intramolecular Michael reaction of methyl ( R)-6-( tert-butoxycarbonylamino)oxy-4-hydroxy-2-hexenoate, in turn obtained from tert-butyl ( R)-3-hydroxy-4-pentenoate, paved the way to the synthesis of both enantiomers of 2-oxa-6-azabicyclo[3.3.0]octan-3-one (the Geissman–Waiss lactone), a precursor for necine bases. Key intermediates in this approach were represented by enantiomeric bicyclic lactones incorporating a [1,2]-oxazinane nucleus, which has been conveniently used to install the pyrrolidine framework of the target compounds through a synthetic scheme featuring the reduction of the nitrogen–oxygen bond and an intramolecular S N2 reaction.

Alternative Synthesis of (-)-Geissman-Waiss Lactone, a Key Intermediate of Necine Bases

A facile synthetic route to (-)-Geissman-Waiss lactone, a key intermediate of necine bases, was established by employing ring closing metathesis (RCM), followed by intramolecular Michael reaction of the resulting α,β-unsaturated lactone, as the key steps.

A novel approach to the Geissman–Waiss lactone and a key intermediate in the synthesis of pyrrolidine trans-lactones

Based on the highly regio- and diastereoselective reductive-ethoxycarbonylmethylation of protected ( S)-malimide 4, a new approach to the Geissman–Waiss lactone 1 and a key intermediate 3 for the synthesis of pyrrolidine trans-lactones (e.g., 2) is described. The synthesis features a one-step and a two-step chemoselective reduction of an amide carbonyl in the presence of an ester group as the key steps.

Reductive decarboxylation of bicyclic prolinic systems: a new approach to the enantioselective synthesis of the Geissman-Waiss lactone. X-ray structure determination of a key lactone intermediate

Two concise and enantioselective syntheses of the necine base precursors (1R,5R)-N-Cbz and N-Boc-2-oxa-6-azabicyclo[3.3.0]octan-3-ones (Geissman-Waiss lactones) were carried out from two enantiomerically pure endocyclic five-membered enecarbamates with overall yields of 23% and 26%, respectively. The synthetic strategy made use of a highly effective and stereoselective [2+2]cycloaddition of enantiomerically pure endocyclic enecarbamates with dichloroketene, as well as an efficient decarboxylation step of a bicyclic alpha-amino acid employing Boger's acyl selenide protocol employing tributyltin hydride. Interesting aspects concerning the regiochemical outcome of Baeyer-Villiger oxidations of bicyclic cyclobutanones are also reported, in which the usual stereoelectronic bias of Baeyer-Villiger oxidation seems to be counterbalanced by steric effects on the putative Criegee intermediate.

ChemInform Abstract: A Dirhodium(II)—Carbenoid Route to (‐)‐ and (+)‐Geissman—Waiss Lactone: Synthesis of (1R,7R,8R)‐(‐)‐Turneforcidine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Development of new reactions and their pharmaceutical application based on the molecular structure characteristics

The author and his group have been developing new reactions based on molecular structure characteristics; sigma-symmetric bifunctional molecules, dipole-dipole repulsion, active amide structures, latent active species, orbital-orbital interactions, nonbonded interactions, strained structures, allenic structures, etc. Various new reactions such as asymmetric aminolyses and Dieckmann-type cyclizations of prochiral sigma-symmetric dicarboxylic diamides, asymmetric aldol-type reactions onto gamma-hydroxybutenolides and asymmetric imine alkylations onto omega-acetoxy lactams using chiral Sn(II) enolates, asymmetric Pummerer-type reactions, cascade reactions and endo-mode cyclizations exploiting alpha,beta-unsaturated allenic esters and ketones, base- and palladium-promoted ring-expansion reactions, and syntheses of alpha-substituted serines and 1-azabicyclo [1.1.0] butane have been achieved. These new reactions were applied to the synthetic development of new seed and lead compounds (SH-enzyme inhibitors, tumor inhibitors, and antibiotics) with the aim of synthesizing new drugs. Asymmetric syntheses of (+)-Prelog-Djerassi lactonic acid methyl ester, (+)-carbacyclin, ISP-I (myriocin), (+)-conagenin, Geissman-Waiss lactone, biapenem (a new carbapenem antibiotic), thienamycin-like gamma-lactam, and bicyclic alkaloids were also achieved by utilizing these reactions. Evaluation and molecular design of the seed and model compounds for angiotensin II receptor antagonists, tumor inhibitors, and antibiotics have been investigated on the basis of QRSA and/or nonbonded S...X (X=O, N, S, halogens) interaction concepts.

A dirhodium(II)-carbenoid route to (-)- and (+)-Geissman-Waiss lactone: synthesis of (1R,7R,8R)-(-)-turneforcidine.

(-)- and (+)-Geissman-Waiss lactone, 4b, was efficiently prepared via the intramolecular C-H insertion reaction of the chiral nonracemic diazoacetates (-)-5a and (+)-5b catalyzed by dirhodium(II) tetrakis[methyl (5R and 5S)-3-phenylpropanoyl-2-imidazolidinone-5-carboxylate]. The cyclization was found to proceed with excellent regioselectivity and cis-diastereoselectivity. The bicyclic lactone (-)-4b was successfully used in the synthesis of the necine base, (-)-turneforcidine 2.

A facile synthesis of (−)- and (+)-Geissman–Waiss lactone via intramolecular Rh(II)-carbenoid mediated C–H insertion reaction: synthesis of (1 R,7 R,8 R)-turneforcidine

The intramolecular C–H insertion reaction in chiral non-racemic diazoacetates (−)- 6 and (+)- 8 catalyzed by chiral Rh 2(MPPIM) 4 proceeded efficiently, with excellent regioselectivity and cis-diastereoselectivity, to give (−)- and (+)-Geissman–Waiss lactone, 4b, respectively. Bicyclic lactone (−)- 4b was used in the synthesis of the necine base (−)-turneforcidine 3.

Regioselective Synthesis of Nitrones by Decarboxylative Oxidation of N-Alkyl-α-amino Acids and Application to the Synthesis of 1-Azabicyclic Alkaloids

Abstract Tungstate-catalyzed oxidation of N-alkyl-α-amino acids with 30% H2O2 solution under phase-transfer conditions gives nitrones regioselectively in good yields. Using this method, stereodivergent synthesis of (R)- and (S)-4-(t-butyldimethylsilyloxy)-1-pyrroline N-oxides ((R)-17a and (S)-17a) was achieved. In addition, (R)- and (S)-3-(t-butyldimethylsilyloxy)-1-pyrroline N-oxides ((R)-45 and (S)-45) were prepared by catalytic oxidation of the corresponding chiral pyrrolidines in a regioselective manner. These chiral cyclic nitrones, 17 and 45 are versatile intermediates for the synthesis of optically active nitrogen heterocycles, since stereoselective additions of carbon nucleophiles to these chiral nitrones can be readily performed. Typically, ZnI2-mediated addition of ketene t-butyldimethylsilyl methyl acetal (29a) to (R)-17a gave the cis-adduct, methyl (2R,4R)-[1,4-bis(t-butyldimethylsilyloxy)pyrrolidin-2-yl]acetate (cis-30). In contrast, the addition of lithium acetylides 34 to the nitrone (R)-17a gave the trans-adducts, (2S,4R)-2-(1-alkynyl)-4-(t-butyldimethylsilyloxy)-1-hydroxypyrrolidines trans-35. These adducts are useful intermediates for syntheses of the nitrogen heterocycles (3R,5R)-1-aza-3-hydroxybicyclo[3.3.0]octane (37) and (6R,8R)-1-aza-8-hydroxybicyclo[4.3.0]nonane (38), respectively. The ZnI2-mediated addition of ketene silyl acetal 29a to the nitrone (R)-45 gave methyl (2S,3R)-[1,3-bis(t-butyldimethylsilyloxy)pyrrolidin-2-yl]acetate (trans-50a), which was used for asymmetric synthesis of the Geissman–Waiss lactone ((−)-49).

Diastereofacial selectivity in ketene [2+2] cycloaddition to endocyclic enecarbamates bearing a chiral auxiliary. Synthesis of the (−)-Geissman-Waiss lactone

The diastereofacial selectivity of enecarbamates bearing a chiral auxiliary was evaluated for the [2+2]cycloaddition with dichloroketenes. Diastereofacial selectivity ranged from zero (bornyl and menthyl) to 60% (Greene's auxiliary and 8-phenylmenthyl). Chromatography separation of the diastereomeric azacyclobutanones derived from the 8-phenylmenthyl enecarbamate permitted an enantiodivergent synthesis of the (−)-Geissman-Waiss lactone, a key intermediate in the synthesis of necine bases.

ChemInform Abstract: Synthesis of (R)‐ and (S)‐3‐(tert‐Butyldimethylsilyloxy)‐1‐pyrroline N‐Oxides — Chiral Nitrones for Synthesis of Biologically Active Pyrrolidine Derivative, Geissman—Waiss Lactone.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of (R)- and (S)-3-(tert-butyldimethylsilyloxy)-1-pyrroline N-oxides — chiral nitrones for synthesis of biologically active pyrrolidine derivative, Geissman-Waiss lactone

Tungstate-catalyzed oxidation of O-tert-butyldimethylsilyl (O-TBDMS) protected (R)-3-hydroxypyrrolidine ((R)-2), derived from trans-4-hydroxy-l-proline, gave O-TBDMS protected (R)-3-hydroxy-1-pyrroline N-oxide ((R)-1), which is a new chiral precursor for the synthesis of Geissman-Waiss lactone. The enantiomeric nitrone (S)-1 was also prepared by the oxidation of (S)-2 derived from l-malic acid.

ChemInform Abstract: 2,5‐Dihydropyrrole Derivatives as Enantiomerically Enriched Building Blocks: Synthesis of the Geissman‐Waiss Lactone and Polyhydroxylated Pyrrolidines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Homoproline homologation by enolate Claisen rearrangement or direct allylation: syntheses of (−)-trachelanthamidine, (−)-isoretronecanol and (±)-turneforcidine

The pyrrolizidine precursors 13 and 14 are obtained both by enolate Claisen rearrangement of the homoproline allyl ester 12 and by direct allylation of N-protected homoproline ethyl ester 15. In both cases, the reactions show poor levels of stereoselectivity. Reduction gives the corresponding alcohols 20a and 21a which are separated and subsequently elaborated to (-)-trachelanthamidine 24 and (-)-isoretronecanol 25 respectively via reductive alkene cleavage, mesylation and spontaneous cyclisation following N-deprotection. The chiral integrity of the original proline-derived asymmetric centre is preserved throughout. A similar enolate allylation gives, with high stereoselectivity, the homologue 34 of the Geissman–Waiss lactone 32, which is similarly transformed into (±)-turneforcidine 31.