Total Syntheses of Kelsoene and Preussin

Basler, Birte; Brandes, Sebastian; Spiegel, Anja; Bach, Thorsten

doi:10.1002/chin.200549262

Cited by 5 publications

(6 citation statements)

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Section: Synthesismentioning

confidence: 99%

“…Owing to its interesting [5.3.0.0 2,5 ]decane structure incorporating six contiguous stereogenic centers including one quaternary carbon center at the C2 position, kelsoene 6 has been the subject of five syntheses to date. 330 The first racemic synthesis of kelsoene 6 was reported in 1999, 331,332 starting from cyclooctadiene 328, which was first transformed into the bicyclooctane 329 in two steps and 67% yield (Scheme 8). Compound 329 was then modified to afford enone 330, allowing introduction of the cyclobutane ring through a [2 + 2] photocycloaddition in the presence of trans-1,2-dichloroethylene to deliver 331 in very good yield (85%).…”

Section: Synthesismentioning

confidence: 99%

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Tricyclic Sesquiterpenes from Marine Origin

et al. 2017

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The structure elucidation, biosynthesis, and biological activity of marine carbotricyclic sesquiterpene compounds are reviewed from the pioneering results to the end of 2015. Their total syntheses with a particular emphasis on the first syntheses, enantiomeric versions, and syntheses that led to the revision of structures or stereochemistries are summarized. Overall, 284 tricyclic compounds are classified into fused, bridged, and miscellaneous structures based on 54 different skeletal types. Tricyclic sesquiterpenes constitute an important group of natural products. Their structural diversity and biological activities have generated further interest in the field of drug discovery research, although the exact mechanisms of action of these species are not well known. Furthermore, these tricyclic structures, according to their chemical complexity, are a source of inspiration for chemists in the field of total synthesis for the development of innovative methodologies.

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Section: Synthesismentioning

confidence: 99%

Section: Synthesismentioning

confidence: 99%

Tricyclic Sesquiterpenes from Marine Origin

et al. 2017

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“…These bioactivities and its unique all-cis structure make it a popular target for total synthesis. More than 30 routes to preussin and (+)-preussin B (a heptyl-substituted analogue) have been reported to date, and five of the total syntheses were reported since 2014. − ,, Syntheses of all eight possible stereoisomers of preussin have also been reported. ,,, Most of these syntheses start with ( l )-phenylalanine derived precursors; after installation of all the substituents in the correct configurations, the linear molecule is then cyclized to form the final pyrrolidine structure. ,,, We hypothesized that we could use our late-stage two-round α-C–H functionalization protocol for a more-flexible approach to preussin analogues. By employing proper Grignard reagents, other alkyl or aryl substitutions can also be easily introduced at the 2- and 5- positions of pyrrolidine.…”

Section: Resultsmentioning

confidence: 99%

Molecular Iodine-Mediated α-C–H Oxidation of Pyrrolidines to N,O-Acetals: Synthesis of (±)-Preussin by Late-Stage 2,5-Difunctionalizations of Pyrrolidine

Rong

Yao

et al. 2017

J. Org. Chem.

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We previously reported an iterative synthesis of unsymmetrical 2,5-disubstituted pyrrolidines from pyrrolidine by two rounds of redox-triggered α-C-H functionalization. Although this approach can be used to introduce substituents at the 2- and 5-positions, it is lengthy because the redox auxiliary must be removed and then reinstalled. Therefore, we sought to develop a method to oxidize 2-functionalized pyrrolidine to cyclic N,O-acetal which could then react with a nucleophile for introduction of the 5-substituent. In this work, we found that molecular iodine can mediate the preferential oxidation of secondary over tertiary α-C-H bonds of α-substituted pyrrolidines to form cyclic N,O-acetals, improving the step economy of our previously reported method. With this strategy, (±)-preussin and its C(3) epimer were synthesized from (±)-pyrrolidin-3-ol.

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“…A large number of these rely on derivatization of readily available chiral pool materials: elaboration of l -phenylalanine facilitated the second synthesis of (+)-preussin that was reported, and this material (or derivatives thereof) has proven to be the most popular starting material by far in subsequent syntheses, − although (in chronological order) d -phenylalanine, d -arabinose, l -aspartic acid, l -pyroglutaminol, , l -serine, , and ( S )-malic acid , (or derivatives thereof) have also been employed as the sources of chirality. Other de novo asymmetric syntheses have been developed, − along with one formal synthesis of (+)-preussin − and two syntheses of (−)-preussin. , Moreover, the synthesis of all eight possible stereoisomers (using an enantiopure phenylalanine derivative as the starting material, proceeding via two nonselective reactions and chromatographic separation) has been reported, − as well as one synthesis of (±)-preussin. , The truncated analogue (+)-preussin B, (2 S ,3 S ,5 R )- N (1)-methyl-2-benzyl-5-(1′-heptyl)pyrrolidin-3-ol (Figure ), was isolated [along with (+)-preussin] in 2014 from Simplicillium lanosoniveum TAMA 173 and was shown to exhibit weak antifungal activity . The first and, to date, the only synthesis of (+)-preussin B to be reported is that of Huang et al, who employed ( S )-malic acid as their starting material .…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (−)-Preussin B, and 3-Deoxy-(+)-preussin B

et al. 2016

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Efficient de novo asymmetric syntheses of (+)-preussin B, the C(2)-epimer of (-)-preussin B, and 3-deoxy-(+)-preussin B have been developed, using the diastereoselective conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl 4-phenylbut-2-enoate and diastereoselective reductive cyclizations of γ-amino ketones as the key steps to set the stereochemistry. Conjugate addition followed by enolate protonation generated the corresponding β-amino ester. Homologation using the ester functionality as a synthetic handle gave the corresponding γ-amino ketone. Hydrogenolytic N-debenzylation was accompanied by diastereoselective reductive cyclization in situ; reductive N-methylation then gave 3-deoxy-(+)-preussin B as the major diastereoisomeric product. Meanwhile, the same conjugate addition but followed by enolate oxidation with (+)-camphorsulfonyloxaziridine gave the corresponding anti-α-hydroxy-β-amino ester. α-Epimerization by oxidation and diastereoselective reduction then gave access to the corresponding syn-α-hydroxy-β-amino ester. Homologation of both of these diastereoisomeric α-hydroxy-β-amino esters gave the corresponding β-hydroxy-γ-amino ketones. N-Debenzylation and concomitant diastereoselective reductive cyclization, followed by reductive N-methylation, provided the C(2)-epimer of (-)-preussin B and (+)-preussin B as the major diastereoisomeric products, respectively. The overall yields (from phenylacetaldehyde) were 19% for 3-deoxy-(+)-preussin B over seven steps, 8% for the C(2)-epimer of (-)-preussin B over nine steps, and 7% for (+)-preussin B over eleven steps.

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Total Syntheses of Kelsoene and Preussin

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 5 publications

References 1 publication

Tricyclic Sesquiterpenes from Marine Origin

Tricyclic Sesquiterpenes from Marine Origin

Molecular Iodine-Mediated α-C–H Oxidation of Pyrrolidines to N,O-Acetals: Synthesis of (±)-Preussin by Late-Stage 2,5-Difunctionalizations of Pyrrolidine

Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (−)-Preussin B, and 3-Deoxy-(+)-preussin B

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