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Stereocontrolled Generation of Benzo[a]-and Indolo[2,3-a]quinolizidines from (S)-Tryptophanol and (S)-(3,4-Dimethoxyphenyl)alaninol-Derived Lactams
European Journal of Organic Chemistry
Abstract
Arantxa Gómez-Esqué, [a] Carmen Escolano, [a] Pedro Florindo, [a] Carlos Ramos, [a] Joan Bosch, [a] and Mercedes Amat* [a] Keywords: Nitrogen heterocycles / Alkaloids / Cyclization / Isomerization / Lactams The stereochemical outcome of Pictet–Spengler cyclizations of (S)-tryptophanol and (S)-(3,4-dimethoxyphenyl)alaninol-derived lactams is discussed. When using HCl the respective trans-H-6/H-12b (or H-11b) indolo[2,3-a]-or benzo[a]quinol-izidines are stereoselectively formed, whereas BF 3 ·Et 2
... The asymmetric synthesis of indoloquinolizidines was achieved starting from enantiopure tryptophanol, a methodology used previously by the groups of Allin [19,20] and Amat-Bosch [21][22][23][24][25][26][27] for the synthesis of several indole alkaloids. In this synthetic strategy, tryptophanol is used not only as the source of chirality, but is also used to incorporate the tryptamine moiety present in the target alkaloids [28,29]. ...
... (6S,12bR)-12-Benzyl-6-(hydroxymethyl)-1,2,3,6,7,12b-hexahydroindolo[2,3-a]quinolizin-4(12H)-one (11). Following the general procedure, and starting from lactam 10 (0.07 g, 0.19 mmol) and 1. 25 (6R,12bS)-12-Benzyl-6-(hydroxymethyl)-1,2,3,6,7,12b-hexahydroindolo[2,3-a]quinolizin-4(12H)-one (13). Following the general procedure, and starting from lactam 12 (0.11 g, 0.32 mmol) and 1.25 M HCl in EtOH (2 mL). ...
Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the syntheses of natural products or biological active molecules containing the aminoalcohol functionality. In this communication, we report the development of a small library of indolo[2,3-a]quinolizidines and evaluation of their activity as N-Methyl D-Aspartate (NMDA) receptor antagonists. The indolo[2,3-a]quinolizidine scaffold was obtained using the following key steps: (i) a stereoselective cyclocondensation of (S)- or (R)-tryptophanol with appropriate racemic δ-oxoesters; (ii) a stereocontrolled cyclization on the indole nucleus. The synthesized enantiopure indolo[2,3-a]quinolizidines were evaluated as NMDA receptor antagonists and one compound was identified to be 2.9-fold more potent as NMDA receptor blocker than amantadine (used in the clinic for Parkinson's disease). This compound represents a hit compound for the development of novel NMDA receptor antagonists with potential applications in neurodegenerative disorders associated with overactivation of NMDA receptors.
... The stereochemical outcome of the Pictet Spengler cyclizations of tryptophanol-derived lactams was later thoroughly investigated by Amat-Bosch's research group. Using the appropriate reaction conditions, a stereocontrolled generation of C-12b epimeric indolo[2,3-a]quinolizidine derivatives was achieved (Scheme 7) [54][55][56]. ...
Corynantheine alkaloids with a tetracyclic indole[2,3-a]-quinolizidine motif are an important issue in academia and in the life science industries due to their broad bioactivity profile. In particular, the main biological effects described for indoloquinolizidines include analgesic, anti-inflammatory, antihypertensive, and antiarrhythmic activities, as well as inhibition of multiple ion channels, affinity for opioid receptors, and activity against Leishmania. For that reason, in the last decades, numerous efforts have been invested in the development of novel synthetic strategies to obtain the indole[2,3-a]-quinolizidine system. This review focuses on the synthetic methodologies developed to target the most important alkaloids of this family, and highlights the potential use of these alkaloids or analogs to treat several diseases, ranging from cancer to neurodegenerative disorders.
Tetracyclic indolo[2,3-a]quinolizidine motifs are an important class of molecules in research and development due to their wide spectrum of biological activities, which include anti-allergic, antibacterial, antiviral, and other bioactive qualities. To develop the indolo[2,3-a]quinolizidine system, innovative synthetic methods have thus attracted tremendous attention during the past decades. This article describes the synthetic approaches developed to target the most important alkaloids of this family, with an emphasis on the possible use of these alkaloids or their analogues to treat a variety of illnesses, ranging from cancer to neurological disorders. In this review article, we have described several crucial synthetic methodologies leading to the indolo[2,3-a]quinolizidine scaffolds. Further, the biological activities and the structure activity relationships (SAR) of such derivatives towards various disease gives a better understanding of the significance of this moiety in medicinal chemistry.
A novel method for joining four components together in a single pot leading to an assortment of N-amino-benzylated phenols is described. The method involves the addition of different Grignard reagents to various o-OBoc salicylaldehydes in the presence of assorted 4,5-dihydrooxazoles, followed by aqueous workup. Seventeen examples are presented with varied (-R, -R' -R″, -R‴, -R⁗, and Cn) substituents.
Synthetic approaches to 5:6:6-fused heterocyclic systems, their reactivity, physical and chemical properties, and applications are reviewed. Both ortho- and peri-fused compounds, which were published between 2008 and early 2019, are discussed. This chapter is divided into sections in accordance to the type of ring conjunction, and each unit consists of linearly and angularly fused systems.
Simultaneous generation of planar, central and axial chiralities on and around a ferrocene backbone via a D-phenylglycinol-induced intramolecular iminium cyclization was disclosed, which is rare and differs from known methods. A series of chiral spiro[cyclopentadienyl 1,2,3,3a-tetrahydropentalenyl iron (II)-1,2ʹ-pyrrolidine] derivatives were prepared in the new method, and their structures characterized unambiguously. The axial chirality caused by the ferrocene backbone and the rigid spiral structure was verified by NOESY and variable temperature NMR experiments, and single-crystal XRD analyses. Mechanism for the stereoselective iminium cyclization reaction was suggested, which was influenced by steric hindrance and hydrogen bonding.
The tetrahydro-β-carboline (THBC) nucleus is a predominant feature of a vast array of naturally occurring alkaloids. Most of these alkaloids have been found to exhibit significant biological activities, which promote to develop a plethora of synthetic methods for the construction of THBCs. In this review, we focus on the recent developments and studies related to the synthesis of THBCs including total syntheses of related alkaloids mainly over the period of 2000–2017. In addition, a brief account of some significant THBC alkaloids with their sources and bioactivities is also presented in tabular format.
N-Allyl tetrahydro-β-carbolines undergo gold-catalyzed cyclizations that lead to tetracyclic compounds, resulting from both ring closure and the transfer of the allylic group from the nitrogen to the carbon backbone. The final skeleton obtained depends on the nature of both the R2 group of the allene and the R3 group of the allylic residue. Mechanistic studies and DFT calculations allowed the determination of all the mechanistic pathways involved in these processes, stemming from a common intermediate that evolves differently according to the substituents nature.
A three-step procedure for the enantioselective synthesis of spiro[indolizidine-1,3′-oxindoles], consisting of a stereoselective cyclocondensation reaction between (S)-tryptophanol and a prochiral or racemic δ-oxoester, bromination of the resulting oxazolopiperidone lactam, and a final stereoselective spirocyclization, is reported.
Enantioenriched N-allyl tetrahydro-β-carbolines were prepared by chiral phosphoric acid-catalyzed Pictet-Spengler reactions. The compounds undergo Pd(0) -catalyzed cyclizations through a tandem deprotection/cyclization process. The regioselectivity of the attack is controlled by the chain length and by the substitution pattern of the allene function. Products resulting from 5-exo- or 6-exo-attack were obtained with diastereoisomeric ratio up to 95:5. Azepinopyrrido[3,4-b]indoles were obtained by 7-endo-cyclizations.
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The diastereoselectivity of the Pictet-Spengler cyclization of bicyclic N-acyliminium ions that contain a 3-azabicyclo[n.3.0]alkane core and an electron-rich π-nucleophilic moiety, such as an indol-2-yl, indol-3-yl, 1-methylpyrrol-2-yl, or 3,5-dimethoxyphenyl group, was examined. The N-acyliminium ions were generated by protonation of the corresponding enamides or hemiaminals, which were derived from imides. Control of the quaternary stereocenter created at the newly formed ring junction was achieved in a diastereodivergent manner by fine-tuning the reaction conditions, which determined whether the reaction proceeded under kinetic or thermodynamic control. Mechanistic studies indicated that a retro-Pictet-Spengler reaction pathway is involved in the equilibration process.
The pallado-catalyzed tandem deprotection/cyclization reaction of enantioenriched N-allyl tetrahydro-β-carbolines on allenes is described. The first step generates in situ a deprotected tetrahydro-β-carboline, which then undergoes a cyclization on the allene function via an intermediate π-allyl Pd(II) derivative. This reaction results in the synthesis of various chiral indolic tetracycles (mainly indolo[2,3a]quinolizidine derivatives) presenting a vinyl function.
A synthetic equivalent of the Nazarov reagent, the silyl derivative 2, able to undergo base-catalyzed double Michael addition reactions with α,β-unsaturated carbonyl compounds has been developed. The new reagent satisfactorily reacts with unsaturated indolo[2,3-a]quinolizidine lactams to give pentacyclic yohimbinone-type derivatives.
Cyclization of the lactam carbonyl on the indole ring in tryptophanol-derived oxazolopiperidone lactams 2 and 6, under the classical POCl3-promoted Bischler-Napieralski conditions and under neutral conditions via the corresponding thiolactam, has been studied. Whereas tricyclic lactam 2 only leads to products coming from an α-amidoalkylation process, bicyclic lactam 6 undergoes cyclization on the lactam carbonyl, leading to the expected indolo[2,3-a]quinolizidine derivatives. Cyclizations on the lactam carbonyl from tryptophanol-derived oxazolopiperidone lactams have been studied. A pyridine ring fused to the piperidone moiety exerts a dramatic effect on the regioselectivity of the cyclization, leading exclusively to α- amidoalkylation products.
In this paper we report a facile and stereoselective approach to the pyrroloisoquinoline ring system through the application of N-acyliminium chemistry from readily available non-racemic chiral templates. The stereochemical outcome of the cyclisation reactions has been determined by NOE and X-ray crystallography. We also demonstrate the synthetic potential of our new approach through removal of the pendant hydroxymethyl auxiliary from a product of cyclisation.
A diverse stereodivergent organocatalytic one-pot addition/cyclization/annulation sequence to optically active quinolizidine derivatives from easily available starting materials is presented. The one-pot sequence relies on a pyrrolidine-catalyzed enantioselective conjugate addition of electron-deficient amide α-carbons to α,β-unsaturated aldehydes, spontaneous hemiaminal formation and acid-catalyzed/mediated N-acyliminium ion cyclization to give the quinolizidine framework. Simple tuning of the reaction conditions in the N-acyliminuim ion cyclization step provides a diastereomeric switch, which gives access to both of the two bridgehead epimers through kinetic, thermodynamic or chelation control. The methodology display a broad substrate scope that is demonstrated by the stereoselective formation of indolo-, thieno-, benzofuro-, furo- and different benzoquinolizidine derivatives with high atom efficiency, up to >99% ee and up to >95:5 dr. Due to its efficiency, synthetic diversity and operational simplicity, this protocol has the potential to find important use as a key step in natural product synthesis, biochemistry and pharmaceutical science. The stereochemical outcome of the one-pot sequence was investigated, and the mechanism and origin of stereoselectivity of the different steps is discussed.
Incluye bibliografía e índice Reimpresión en 1984, 1986, 1989.
We report a novel, facile and stereoselective approach to the pyrroloisoquinoline ring system from readily available, non-racemic, bicyclic lactam substrates.
A new approach to the benzo[a]quinolizidine alkaloid was described. Total synthesis of (±)-protoemetinol (1) was reported.
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The synthetic potential of enantiopure (3R,6S,8aS)-(-)-6-methyl-3-phenylhexahydrooxazolo[3,2-a]pyridin-5-one 2 is illustrated by a short synthesis of the 5,8-disubstituted indolizidine alkaloid (+)-209B.
We describe the transformation of (R)-(-)-1-(2'-hydroxy-1'-phenylethyl)piperidin-2-one 1 into (R)-(-)-3-phenyl-2,3,5,6,7,8-hexahydro-oxazolo[3,2-a]pyridin-4-ylium bromide 2 using POBr 3 . Reduction of 2 with Red-Al at -78 °C gave (3R,8aR)-(-)-3-phenylhexahydro-2H-oxazolo[3,8-a]-pyridine 3 as a single diastereoisomer. The synthetic potential of these transformation is illustrated by the enantiopure synthesis of (S)-(+)-coniine, (R)-(-)-coniceine and (R)-(+)-anabasine.
The acid-catalysed C-3 epimerization of the indole alkaloid reserpine (1) and other closely related indolo[2,3-a]quinolizidines is reviewed. The three mechanisms that have been proposed and relevant experimental findings are discussed. Representative examples of C-3 epimerization reactions are included.
A survey of the utilitarian bicyclic lactams is presented, These chiral templates have provided, and continue to provide, access to a plethora of natural and unnatural carbocyclic products in high enantiomeric purity, Their synthetic versatility has recently grown with the development of new methods for the construction of heterocycles, In addition to the cyclopentenone, cyclohexenone and hexahydroindenone systems, products derived from bicyclic lactams now include optically active piperidines, pyrrolidines, pyrrolidinones and tetrahydroisoquinolines. These favourable properties make the bicyclic lactams highly adaptable tools for asymmetric synthesis.
The key chiral nonracemic 4,4-disubstituted 2-butyrolactone carboxylic acid, (S)-4, is readily accessible via an efficient and stereospecific dirhodium(II) tetraacetate catalyzed tertiary C-H insertion reaction of the diazomalonate (S)-5. The coupling of the acid (S)-4 with tryptamine produces the amide (S)-3, which is then transformed into the aldehyde 23 and hydroxy-lactam 24. Acid-mediated Pictet-Spengler cyclization of 23 and 24 produces the tetracyclic indole lactams (1S,12bS)-25a and (1S,12bR)-25b. Compounds 25a and 25b are converted, via the lactam alcohols 30a and 30b, to (-)-eburnamonine (1a) and (+)-epi-eburnamonine (1b).
The compounds (3R,5S)-(+)-5-methyl-3-phenyl-2,3,5,6,7,8-hexahydro-oxazolo[3,2-a]pyridin-4-ylium iodide 4 and (3R,5S)-(+)-5-n-propyl-3-phenyl-2,3,5,6,7,8-hexahydro-oxazolo[3,2-a]pyridin-4-ylium iodide 5 were synthesized in two steps starting from the bicyclic thiolactam trans (3R,2aS)-(−)-5-thio-3-phenyl-2,3,6,7,8,2a-hexahydro-oxazolo[3,2-a]pyridine 1. In addition, starting from 5 an enantiospecific synthesis of (+)-coniine 7 was achieved.
We report a novel, facile and stereoselective approach to a tricyclic tetrahydroisoquinoline ring system from readily available, non-racemic, bicyclic lactam substrates.
Stereocontrolled N-acyliminium ion cyclisation of L-DOPA derived succinimide 5 has been investigated. Addition of organolithiums to chiral non-racemic 5 yields oxoamides, which are cyclised diastereoselectively upon treatment with BF3·OEt2, to afford 5,10b-trans pyrroloisoquinolones in moderate yields and high ee (99%).
The regioselective reduction of a range of N-substituted-4,4-dimethylhomophthalimide derivatives gave the related carbinol amides that function as acyliminium ion precursors in the presence of Lewis or protic acids; the fate of the acyliminium ions is determined in part by the nucleophilicity of the β-arylethyl group on nitrogen, the electrophile used to generate the ion, and the precise reaction conditions and led either to cyclisation reactions or methyl migration.
The role of the nitrogen lone pairs in the mechanism of the acid-catalysed epimerization of indolo[2,3-a]quinolizidines is investigated using lactams as model compounds. Deethyleburnamonine (3) did not epimerize with trifluoroacetic acid (TFA), whereas deethyldihydroeburnamenine (7) underwent epimerization smoothly. Under treatment with TFA, lactams 12 and 13 both epimerized with ease to a mixture of lactams 12 and 13. An analogous equilibrium was achieved when the experiment was repeated with lactams 18 and 19. Intermediate 20 was trapped (Zn reduction) in the acid-catalysed epimerization of lactam 12, allowing conclusions about the mechanism.
Acid-catalysed epimerization of 1-, 2- and 3-monosubstituted 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine alkyl derivatives in refluxing trifluoroacetic acid (TFA) leads to an equilibrium mixture of C-12b diastereomers. The thermodynamically more stable epimer predominates over the kinetically favoured epimer in a ratio of about 85:15 unless the substituent is at C-1, in which case the ratio is 55:45. The proton at C-12b is exchanged when the epimerization is performed in refluxing TFA-d. New stereoselective synthesis of the missing 2-ethylindolo[2,3-a]quinolizidines is described.
Das biogenetisch interessante, octacyclische Indolalkaloid Roxburghin D kann, ausgehend von einem sterisch einheitlichen Zwischenprodukt, stereoselektiv aufgebaut werden. Der sterische Verlauf der entscheidenden Cyclisierungsreaktion wird unter Verwendung von Modellsubstanzen geklärt.
Reactions with Indole Derivatives, XXV, The Stereoselective Total Synthesis of Roxburghin D
The biogenetically interesting, octacyclic indole alkaloid roxburghin D can be synthesized stereoselectively from a configuratively pure intermediate. The steric course of the decisive cyclisation reaction is disclosed by means of model substances.
Some time ago, Siddiqui et al. proposed structure 1 for the naturally occurring indole alkaloid yohambinine, which they had isolated from Rauwolfia serpentinaBenth. In the present paper, enantioselective syntheses of all eight diastereoisomers endowed with the proposed 5-methylyohimbane structure are disclosed. However, none of the synthetically prepared compounds showed spectroscopic properties identical with those reported for the natural product yohambinine, which, therefore, must possess an altogether different constitutional formula. The ground-state conformations of the diastereoisomers 1, 14, 18, 19, 21, 22, 25, and 26 were deduced by spectroscopic methods, and the outcome was compared with the results of extensive force-field, semi-empirical, and ab-initio calculations.
Enaminoesters containing a tethered indole or aryl moiety on the amine react with substituted maleic anhydrides or acryloyl chlorides to provide pyrrolinone or dihydropyridone products, respectively. The indole-tethered dihydropyridones can be induced to undergo a one-pot cyclization whereas, the indole-tethered pyrrolinone intermediates are readily cyclized with HCl. The aryl-tethered pyrrolinones or dihydropyridones can be isolated and subsequently induced to cyclize with triflic acid. This methodology culminates in the synthesis of erythrane-like and other natural products that are readily amenable to combinatorial library production.
The details of an efficient synthesis of (±)-quebrachamine and a formal synthesis of (±)-tabersonine via the cleavage of a cyclic α-diketone monothioketal are described.
Condensation of racemic keto-ester 2 and 1.1 equiv of (R)-(−)-phenylglycinol in toluene with azeotropic removal of water and methanol gave rise to a tetracyclic lactam in greater than 90% yield. Examination of the crude reaction product by 1H and 13C NMR, capillary GC, and HPLC revealed this product to be a single isomer, the absolute configuration of which was determined to be that illustrated by structure 3. The tetracyclic lactam 3 was stereospecifically reduced to either the cis-fused bicyclic pyrrolidine 4 or the cis-fused bicyclic pyrrolidinone 9. The chiral auxiliaries in both 4 and 9 were removed using different, novel methodologies. This highly stereoselective reaction establishes two contiguous chiral centers via the deracemization of an achiral keto-ester. This methodology has been applied to the synthesis of (1R,5R)-2-azabicyclo[3.3.0]octane 15. This important amine is now readily available from commercial materials in only three steps.
Expeditious enantioselective syntheses of (+)-quebrachamine (6), (-)-aspidospermidine (7), (+)-demethoxyaspidospermine (8), and (-)-eburnamonine (9) were accomplished starting from (S)-lactone 1. The syntheses also complete formal, total syntheses of 12 other indole alkaloids of the Aspidosperma and Hunteria types. The key step in the synthesis of (+)-quebrachamine (6) was the Pictet-Spengler condensation of chiral C9 unit 10, derived from 1, with tryptamine. Another C9 unit (15) was also prepared from 1 and utilized for the syntheses of three other alkaloids, 7, 8, and 9.
N-Acyliminium cyclizations onto benzenoid rings to give tetrahydroisoquinoline ring systems were studied. Particular attention was paid to the stereochemical effect of substituents present on the isoquinoline ring. High stereoselectivity (≥90%) was observed with aryl substituents at (local) 4 and 3 positions of the isoquinoline ring (e.g., 2 → 3 and 30 → 31). In addition to cyclizations onto benzenoid rings, some cyclizations onto heterocycles (pyrrole, thiophene, indole) were examined. Base-induced equilibration of isomer pairs was performed to obtain relative stabilities. The cyclizations were determined to be kinetic in nature. A discussion of our iminium cyclizations and relevant examples from the literature is presented.
Fused β-carboline systems, as indolo[2,3-a]indolizidinones, indolo[2,3-a]quinolizidinones, their 2-oxa analogues, and benzo[a]indolo[2,3-a]indolizidinones are prepared efficiently via an RLi addition-N-acyliminium ion cyclisation sequence on readily available imides. In an enantioselective variant of these α-amidoalkylation reactions, the addition of MeLi to a chiral non-racemic imide derived from tryptophan yielded an oxo amide, which was cyclised diastereoselectively upon treatment with BF3·OEt2, to afford 5,11b-trans-indoloindolizidinone in moderate yield and high ee (99%).
The chiral non-racemic bicyclic lactam has proven to be an exceptionally versatile chiral template for the asymmetric construction of a variety of optically pure compounds. Those lactams derived from keto acids have been applied to the synthesis of a host of natural products and pharmacologically interesting heterocycles and carbocycles. A variety of mechanistic questions regarding facial stereo-control have been investigated using the chiral template as the key probe. However, further elucidation of the subtle mechanistic principles involved await further study.
(Chemical Equation Presented) We report a novel, facile, and asymmetric approach for the synthesis of polycyclic benzo[a]quinolizidine targets. In the formation of more functionalized derivatives, we have observed the generation of an iminium ether salt intermediate, formed during an unprecedented retro-Diels-Alder/N-acyliminium cyclization cascade. The iminium ether intermediate was isolated in good yield, characterized by X-ray crystallography, and subsequently applied as a synthetic building block.
The epimerization at C3 of reserpine and deserpidine catalysed by acetic acid has been studied. 3-Deuterio-isoreserpine epimerizes without loss of label. Reserpine and isoreserpine methosalts do not epimerize at C3 in acetic acid. 3-Deuterio-isodeserpidine dedeuterates faster than it epimerizes. It is concluded that epimerization in these alkaloids involves initial C2 protonation according to Scheme II.
For Abstract see ChemInform Abstract in Full Text.
The four-component coupling-amination-aza-annulation-Pictet-Spengler (CAAPS) sequence of acid chlorides 1, terminal alkynes 2, tryptamine derivatives 6, and acryloyl chloride derivatives 4 represents a facile and rapid one-pot access to tetrahydro-beta-carbolines 7 in moderate to good yields.
We report a novel, facile and asymmetric approach to both enantiomers of the indole alkaloid deplancheine from a readily available, nonracemic chiral template. The natural product and its antipode are isolated with >95% ee.
[reaction: see text] Stereocontrolled intramolecular alpha-amidoalkylation reactions of L-DOPA-derived succinimides have been studied. Addition of MeLi to nonracemic succinimides 9a-d yields oxoamides, which are cyclized upon treatment with Lewis or protic acids to afford (5S,10bS)-trans 11 or (5S,10bR)-cis 12pyrroloisoquinolines with variable diastereoselectivities, but with high enantiomerical purities (ee 99%).
An enantioselective two-step route to substituted benzo[a]- and indolo[2,3-a]quinolizidines has been developed. It consists of (i) a stereoselective cyclocondensation of a racemic or prochiral delta-oxo(di)ester with either (S)-(3,4-dimethoxyphenyl)alaninol or (S)-tryptophanol in a process involving a dynamic kinetic resolution and/or the differentiation of enantiotopic or diastereotopic ester groups, and (ii) a subsequent stereocontrolled cyclization on the aromatic ring taking advantage of the masked N-acyl iminium ion present in the resulting oxazolopiperidone lactams.
For Abstract see ChemInform Abstract in Full Text.
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13 C NMR (400 MHz, DMSO): δ = 18
- Hz
Hz, 1 H, ArH), 10.92 (s, 1 H, N-H) ppm. 13 C NMR (400 MHz,
DMSO): δ = 18.0 (C-1), 21.1 (C-7), 27.9 (C-2), 32.5 (C-3), 52.7 (C-
12b), 55.1 (C-6), 61.8 (CH 2 O), 106.5 (C AR ), 111.6 (CH AR ), 118.1
(CH AR ), 119.0 (CH AR ), 121.2 (CH AR ), 127.2 (C AR ), 133.8 (C AR ),
136.7 (C AR ), 172.3 (NCO) ppm. IR (neat): ν ˜ = 3300 (OH, NH),
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