Spirocyclic Restriction of Nucleosides. Synthesis of the First Exemplary <i>s</i><i>yn</i>-1-Oxaspiro[4.4]nonanyl Member

Paquette, Leo A.; Bibart, Richard Todd; Seekamp, Christopher K.; Kahane, Alexandra L.

doi:10.1021/ol010209x

Cited by 33 publications

(10 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A survey of the Cambridge Structural Database (July 2004 update, Version 5.25;Allen, 2002) revealed that this is the ®rst structure comprising these two fused heterocyclic rings with a carbonyl O atom at the 1-position and a methoxy group at the 3-position. The bond lengths and angles in (I) are well within the ranges reported for 4-methoxy-5-methylpyrimidin-2-ones (Brennan et al, 1986;Paquette et al, 2001) and piperidin-3-ols (Herdeis et al, 1996;Kirfel et al, 1996). As expected, the exception is the N9ÐC10 bond, which in (I) is signi®cantly shorter (ca 0.09 A Ê ) than the corresponding bond in the piperidin-3-ols, due to the delocalization effect of the pyrimidine ring.…”

supporting

confidence: 82%

Hydrogen-bonding and C—H...π interactions in 7-hydroxy-3-methoxy-4-methyl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidin-1(9H)-one

et al. 2005

View full text Add to dashboard Cite

In the title compound, C10H14N2O3, a pyrimidine ring is fused with a piperidine ring. The pyrimidine ring is planar, whereas the piperidine ring adopts a half-chair conformation. The molecules of the title compound are connected via O-H...O intermolecular hydrogen bonds into infinite zigzag chains. The pyrimidine ring is involved in three C-H...pi interactions, which link the hydrogen-bonded chains into a three-dimensional framework.

show abstract

supporting

confidence: 82%

Hydrogen-bonding and C—H...π interactions in 7-hydroxy-3-methoxy-4-methyl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidin-1(9H)-one

et al. 2005

View full text Add to dashboard Cite

show abstract

“…An appropriately protected dihydrofuran 88 is a convenient substrate for the construction of the riboside 94 (Scheme 19). 30 Allylic oxidation using pyridinium chlorochromate, chromium trioxide, 3,5-dimethylpyrazole (3,5-DMP), and 4-Å molecular sieves at -20 °C affords the unsaturated γ-lactone 89 in 91% yield. Osmium tetroxide catalyzed dihydroxylation in the presence of N-methylmorpholine N-oxide provides the ribose derivative 90 in a highly diastereoselective manner in 93% yield.…”

Section: Scheme 18mentioning

confidence: 99%

“…The methoxymethyl substituent sterically, and perhaps electronically, impacts this process to render it highly diastereoselective. 30 In a subsequent one-pot reaction, the lactone carbonyl group of 90 is reduced with diisobutylaluminum hydride and the…”

Section: Scheme 18mentioning

confidence: 99%

Stereoselective Reactions in Preparation of Chiral α-Heteraspiro[m.n]alkanes

Undheim

2015

Synthesis

View full text Add to dashboard Cite

The biological importance and wide occurrence of spirane systems in nature have stimulated studies in spirane chemistry. The fundamental spirane framework consists of two monocyclic rings linked in an orthogonal relationship by a common ring carbon. This review covers families of annular α-monoheteraspiranes starting with α-heteraspiro[2.4]heptanes and terminating with α-hetera[5.6]dodecanes; the annular heteroatoms are N, O, or S. The spirane systems are arranged according to the relative size of the two monocyclic rings with highest priority for the smaller ring, Often optically active spiranes are prepared for biological reasons by chemical modifications of natural products related to the spirane to be prepared. Chiral auxiliaries are useful in the introduction and control of stereochemistry in the construction of spiranes as intermediates in the preparation of novel amino acids and nucleosides. Another aspect of chiral spirane chemistry concerns modifications and conformational restrictions introduced in natural carbohydrates, nucleosides, and amino acids. 1 Introduction 2 Heteraspira[2.m]alkanes 3 Heteraspira[3.m]alkanes 4 Heteraspira[4.m]alkanes 5 Heteraspira[5.m]alkanes Key words α-heteraspiranes, chirons, stereoselective syntheses, spiroannulations, spirocyclic amino acids, spirocyclic nucleosides 2 Heteraspiro[2.m]alkanes 2.1 Heteraspiro[2.4]heptanes 2.1.1 4,6-Diazaspiro[2.4]heptane The Seebach chiron, tert-butyl (2S)-2-tert-butyl-3methyl-4-oxoimidazoline-1-carboxylate, was developed for the stereoselective construction of α-amino acids. 11 The chiron has also been used for the stereoselective synthesis of cyclic amino acids via a spirane. During lithiation of tertbutyl (2S)-2-tert-butyl-3-methyl-4-oxoimidazoline-1-carboxylate at the 5-position, the tert-butyl substituent effectively shields one face of the ylide from electrophilic attack. Thus acetate 1 (Scheme 1) is available from lithiated Seebach chiron and methyl α-bromoacetate. In a synthesis of 1-amino-2,2-dideuteriocyclopropane-1-carboxylic acid (4) via spirane 3, substrate 1 is stepwise lithiated by lithium

show abstract

“…An as yet relatively unexplored strategy for conformational restriction is the synthesis of spironucleosides. A 2Ј-spirocyclopropane derivative of 2Ј-deoxyadenosine has been synthesized as a mechanistic probe for ribonucleotide reductases, 16 and 1Ј-spiro-17 , 3-spiro- 18 and 4Ј-spiro 19 ribonucleoside derivatives have been prepared as conformationally restricted derivatives. Herein we introduce 2Ј-spironucleoside derivatives (2Ј-C,2Ј-O-propano-and 2Ј-C,2Ј-O-ethano nucleosides) as novel conformationally restricted probes.…”

Section: Introductionmentioning

confidence: 99%

2′-Spiro ribo- and arabinonucleosides: synthesis, molecular modelling and incorporation into oligodeoxynucleotides

et al. 2003

View full text Add to dashboard Cite

We have synthesized four conformationally restricted bicyclic 2'-spiro nucleosides via 2'-C-allyl nucleosides as key intermediates. The ribo-configured 2'-spironucleosides 9b and 14b were obtained by a convergent strategy starting from 2-ketofuranose 1 whereas the arabino-configured 2'-spironucleosides 21 and 27 were obtained by a linear strategy with a 2'-ketouridine derivative as starting material. The furanose ring of 9b/14b adopts N-type conformations whereas the furanose ring of 21/27 exists as an N<==>S equilibrium. These compounds showed no anti-HIV-1 activity or cytotoxicity. Incorporation of the four 2'-spironucleosides (as monomers X4 and X5) into oligodeoxynucleotides was accomplished using the phosphoramidite approach on an automated DNA synthesizer. Irrespective of monomeric configuration, hybridization studies revealed that these 2'-spironucleotide monomers (X4 and X5) induce decreased duplex thermostabilities compared with the corresponding DNA:DNA and DNA:RNA duplexes. Molecular modelling indicated that steric constraints are a possible reason for the lowered binding affinities of the modified oligodeoxynucleotides towards complementary single-stranded DNA and single-stranded RNA complements.

show abstract

Spirocyclic Restriction of Nucleosides. Synthesis of the First Exemplary syn-1-Oxaspiro[4.4]nonanyl Member

Cited by 33 publications

References 32 publications

Hydrogen-bonding and C—H...π interactions in 7-hydroxy-3-methoxy-4-methyl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidin-1(9H)-one

Hydrogen-bonding and C—H...π interactions in 7-hydroxy-3-methoxy-4-methyl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidin-1(9H)-one

Stereoselective Reactions in Preparation of Chiral α-Heteraspiro[m.n]alkanes

2′-Spiro ribo- and arabinonucleosides: synthesis, molecular modelling and incorporation into oligodeoxynucleotides

Contact Info

Product

Resources

About

Spirocyclic Restriction of Nucleosides. Synthesis of the First Exemplary syn-1-Oxaspiro[4.4]nonanyl Member

Cited by 33 publications

References 32 publications

Hydrogen-bonding and C—H...π interactions in 7-hydroxy-3-methoxy-4-methyl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidin-1(9H)-one

Hydrogen-bonding and C—H...π interactions in 7-hydroxy-3-methoxy-4-methyl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidin-1(9H)-one

Stereoselective Reactions in Preparation of Chiral α-Hetera­spiro[m.n]alkanes

2′-Spiro ribo- and arabinonucleosides: synthesis, molecular modelling and incorporation into oligodeoxynucleotides

Contact Info

Product

Resources

About

Stereoselective Reactions in Preparation of Chiral α-Heteraspiro[m.n]alkanes