Synthesis of Conduramines from<i>N</i>-<i>tert</i>-Butoxycarbonylpyrrole

Leung-Toung, Régis; Liu, Yanzhou; Muchowski, Joseph M.; Wu, Yulin

doi:10.1021/jo971907r

Cited by 55 publications

(28 citation statements)

References 69 publications

(37 reference statements)

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“…General information (2S, 5R)-2-Isopropyl-5-methylcyclohexyl 1H-pyrrole-1-carboxylate was prepared according to a literature procedure [15]. Commercial reagents were used without further purification unless otherwise indicated.…”

Section: Methodsmentioning

confidence: 99%

Acylation of Tropane Alkaloids Displaying Reversed Diastereoselectivities under Enzymatic versus Chemical Conditions

Affolter¹,

Baro²,

Laschat

et al. 2007

Zeitschrift Für Naturforschung B

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Lipase-mediated monoacetylation of 6,7-dihydroxytropinones 4 gave acetates 5, ent-5 which were analyzed as Mosher esters 9a, b by 1 H NMR spectroscopy. However, the hydroxy groups in 4 were not differentiated by lipases. Reduction of the keto function and subsequent silylation afforded a mixture of endo/exo-TBS ethers 11, which were dihydroxylated to give the corresponding diols endo/exo-12. In chemical acetylation a change of the endo/exo ratio in favor of the endo-derivative endo-13 was observed, whereas the formation of the exo-acetate exo-13 dominated in lipase-catalyzed acylation reactions. A mechanistic proposal is given.

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Section: Methodsmentioning

confidence: 99%

Acylation of Tropane Alkaloids Displaying Reversed Diastereoselectivities under Enzymatic versus Chemical Conditions

Affolter¹,

Baro²,

Laschat

et al. 2007

Zeitschrift Für Naturforschung B

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“…7 On the other hand, although epoxysulfones are versatile synthons, particularly in the presence of nucleophilic reagents, 8 the chemistry of strained a,b-epoxysulfones such as 2 and 3 ( Figure 2) remains almost unexplored 9 despite the rich functionality present in these compounds.…”

Section: Methodsmentioning

confidence: 99%

Straightforward Synthesis of Strained α,β-Epoxysulfones via Epoxidation of Vinylsulfones Using N-Methylmorpholine N-Oxide as Epoxidizing Reagent

Rincón¹,

Aljarilla²,

Criado³

et al. 2007

Synlett

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An efficient, stereoselective route to the a,b-epoxysulfones using N-methylmorpholine N-oxide (NMO) as epoxidizing reagent is described.The oxa-and azanorbornenic vinylsulfones 1 (Figure 1) are useful intermediates for the synthesis of substituted cyclohexane and cyclohexene derivatives via regio-and stereocontrolled ring-opening reactions. 1 Figure 1In particular, the nucleophilic (Michael) addition of organometallic reagents followed by b-elimination of the resulting arylsulfonyl-stabilized carbanion occurs with concomitant bridge opening 2 (Scheme 1) due to the strained character of the bicyclic system. Scheme 1This methodology has become a key step for the synthesis of compounds such as 7-deoxypancratistatin, 3 several carbasugars, 4 analogues of a ring of vitamin D 3 , 5 polypropionate (stereotetrads) fragments 6 and analogues of conduramines. 7On the other hand, although epoxysulfones are versatile synthons, particularly in the presence of nucleophilic reagents, 8 the chemistry of strained a,b-epoxysulfones such as 2 and 3 ( Figure 2) remains almost unexplored 9 despite the rich functionality present in these compounds.Usually these epoxysulfones have been synthesized by the nucleophilic epoxidation of a,b-unsaturated sulfones with t-BuOOLi, among other epoxidizing reagents. 10 Figure 2In the search for an alternative method, we speculate that if the Michael addition described in Scheme 1 could be carried out using a nucleophilic oxygen atom attached to a good leaving group, the elimination step may occur on this leaving group, thereby leaving the bicyclic skeleton intact and allowing for the synthesis of epoxysulfones such as 2 and 3 (Scheme 2). Scheme 2Assuming the exo attack of the nucleophilic reagent on the bicyclic system, 11 the exo stereochemistry of the oxirane functionality (endo-sulfone) remains secure. In this context an amine oxide constitutes an excellent candidate for testing this assumption. 12 In this way, vinylsulfones 4-8 ( Figure 3) were prepared 13 and treated with N-methyl-NR R 2 ArO 2 S X 1 ArO 2 S X R 1 ArO 2 S R 1 XM R 1 M (Michael) β-elimination R 2 R 2 R 2 X O SO 2 Ar 2a X = O 2b NR 2c CH 2 X O SO 2 Ar 3a X = O 3b NR X ArO 2 S X ArO 2 S O LG X O SO 2 Ar LG-O 2, 3

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“…Dihydroxylation of 6 with OsO 4 /NMO cleanly led to the exo-cis-diol 11 (100%) [48], and Williamson ether synthesis (2-(bromomethyl)naphthalene/NaH) provided mono-ether (AE)-12 (68%) together with di-ether 13 (16%) (Scheme 3 2.3. Biological Activity.…”

mentioning

confidence: 99%

Development of a New Class of Inhibitors for the Malarial Aspartic Protease Plasmepsin II Based on a Central 7‐Azabicyclo[2.2.1]heptane Scaffold

Carcache¹,

Hörtner²,

Seiler³

et al. 2003

Helvetica Chimica Acta

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Dedicated to Professor Andrea Vasella on the occasion of his 60th birthdayPlasmepsin II (PMII), a malarial aspartic protease involved in the catabolism of hemoglobin in parasites of the genus Plasmodium, and renin, a human aspartic protease, share 35% sequence identity in their mature chains. Structures of 4-arylpiperidine inhibitors complexed to human renin were reported by Roche recently. The major conformational changes, compared to a structure of renin, with a peptidomimetic inhibitor were identified and subsequently modeled in a structure of PMII (Fig. 1). This distorted structure of PMII served as active-site model for a novel class of PMII inhibitors, according to a structure-based de novo design approach (Fig. 2). These newly designed inhibitors feature a rigid 7-azabicyclo[2.2.1]heptane scaffold, which, in its protonated form, is assumed to undergo ionic H-bonding with the two catalytic Asp residues at the active site of PMII. Two substituents depart from the scaffold for occupancy of either the S1/S3 or S2'-pocket and the hydrophobic flap pocket, newly created by the conformational changes in PMII. The inhibitors synthesized starting from N-Boc-protected 7-azabicyclo[2.2.1]hept-2-ene (6; Schemes 1 ± 5) displayed up to single-digit micromolar activity (IC 50 values) toward PMII and good selectivity towards renin. The clear structureÀactivity relationship (SAR; Table) provides strong validation of the proposed conformational changes in PMII and the occupancy of the resulting hydrophobic flap pocket by our new inhibitors.

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Synthesis of Conduramines fromN-tert-Butoxycarbonylpyrrole

Cited by 55 publications

References 69 publications

Acylation of Tropane Alkaloids Displaying Reversed Diastereoselectivities under Enzymatic versus Chemical Conditions

Acylation of Tropane Alkaloids Displaying Reversed Diastereoselectivities under Enzymatic versus Chemical Conditions

Straightforward Synthesis of Strained α,β-Epoxysulfones via Epoxidation of Vinylsulfones Using N-Methylmorpholine N-Oxide as Epoxidizing Reagent

Development of a New Class of Inhibitors for the Malarial Aspartic Protease Plasmepsin II Based on a Central 7‐Azabicyclo[2.2.1]heptane Scaffold

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