- Synthesis of the transfer-RNA nucleoside queuosine by using a chiral allyl azide intermediate
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Chilled out: Chiral allyl azides are rarely used in natural product synthesis because of their tendency to undergo a [3.3] sigmatropic rearrangement (see scheme, top). In allylic cyclopentenyl azides, this rearrangement can be suppressed at just 0°C, enabling a short convergent synthesis of the hypermodified transfer-RNA nucleoside queuosine. (Chemical Equation Presented).
- Klepper, Florian,Jahn, Eva-Maria,Hickmann, Volker,Carell, Thomas
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- Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development
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Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y12 and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise understanding of metabolite activity and stereochemistry, and a lack of acceptable analytes for quantifying in vivo metabolite formation. Methods for the production of all bioactive metabolites of clopidogrel, their stereochemical assignment, and the development of stable analytes via three conceptually orthogonal routes are disclosed. (Chemical Equation Presented).
- Shaw, Scott A.,Balasubramanian, Balu,Bonacorsi, Samuel,Cortes, Janet Caceres,Cao, Kevin,Chen, Bang-Chi,Dai, Jun,Decicco, Carl,Goswami, Animesh,Guo, Zhiwei,Hanson, Ronald,Humphreys, W. Griffith,Lam, Patrick Y. S.,Li, Wenying,Mathur, Arvind,Maxwell, Brad D.,Michaudel, Quentin,Peng, Li,Pudzianowski, Andrew,Qiu, Feng,Su, Shun,Sun, Dawn,Tymiak, Adrienne A.,Vokits, Benjamin P.,Wang, Bei,Wexler, Ruth,Wu, Dauh-Rurng,Zhang, Yingru,Zhao, Rulin,Baran, Phil S.
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- Improved and alternative synthesis of D- and L-cyclopentenone derivatives, the versatile intermediates for the synthesis of carbocyclic nucleosides
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Improved and alternative syntheses of D- and L-cyclopentenone derivatives were achieved in six steps from D-ribose via ring-closing metathesis (RCM) reaction as a key step. These derivatives serve as very versatile intermediates for the synthesis of carbocyclic nucleosides.
- Moon, Hyung Ryong,Choi, Won Jun,Kim, Hea Ok,Jeong, Lak Shin
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- Antiviral activity of cyclopentenyl nucleosides against orthopox viruses (smallpox, monkeypox and cowpox)
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An improved method for the synthesis of enantiomerically pure D-cyclopentenyl nucleosides has been accomplished and their antiviral activity against orthopox viruses have been evaluated. The key intermediate, L-cyclopent-2-enone 13 was prepared from D-ribose using a ring closing metathesis reaction in eight steps. Among the synthesized nucleosides, the adenine 2 (Neplanocin A), cytosine 14, and 5-F-cytosine 15 analogues exhibited potent anti-orthopox virus activity, including smallpox virus.
- Chu,Jin,Baker,Huggins
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- A NEW ROUTE TO (+)-2,3-(ISOPRPOPYLIDENEDIOXY)-4-CYCLOPENTENONE VIA THE OPTICALLY ACTIVE DICYCLOPENTADIENE INTERMEDIATE
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Chiral synthesis of the dicyclopentadiene derivative and its stereoselective conversion into (+)-2,3-(isoprpylidenedioxy)-4-cyclopentenone, a versatile building block for the synthesis of cyclopentanoid natural products, have been described.
- Takano, Seiichi,Inomata, Kohei,Ogasawara, Kunio
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- EFFICIENT ENANTIOSELECTIVE SYNTHESES OF CARBOCYCLIC NUCLEOSIDE AND PROSTAGLANDIN SYNTHONS
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Simple and efficient enantioselective syntheses of two hydroxylated cyclopentenones, 2 and 10, which are useful intermediates for the synthesis of various carbocyclic nucleosides and prostaglandins, directly from readily available sugars are described.
- Ali, Syed Mashhood,Ramesh, Kakarla,Borchardt, Ronald T.
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- Improved practical synthesis of a prostaglandin and carbocyclic nucleoside synthon
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An efficient, four step synthesis of chiral enone 2a [(+)-2,3-(isopropylidenedioxy)-4-cyclopentenone] from diol 1a (X = Cl), available from microbial oxidation of chlorobenzene, is described. This synthesis is a vast improvement over that previously reported and compares very favorably with others in the literature.
- Hudlicky,Natchus,Nugent
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- USE OF THE IRRITATING PRINCIPAL OLEOCANTHAL IN OLIVE OIL, AS WELL AS STRUCTURALLY AND FUNCTIONALLY SIMILAR COMPOUNDS
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The invention provides oleocanthal analogs and methods of using oleocanthals in various formulations including, food additives; pharmaceuticals; cosmetics; animal repellants; and discovery tools for mammalian irritation receptor genes, gene products, alleles, splice variants, alternate transcripts and the like.
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Page/Page column 16
(2011/02/18)
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- A short, concise synthesis of queuine
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A short, concise synthesis of queuine was accomplished in a 36% overall yield through a convergent scheme utilizing a reductive amination as the penultimate step. The synthesis demonstrates the utility of silylation to facilitate reactions of various pyrrolo[2,3-d]pyrimidine intermediates, and offers the possibility of easily accessing related pyrrolo[2,3-d]pyrimidines as well as making additional analogues of queuine.
- Brooks, Allen F.,Garcia, George A.,Showalter, H.D. Hollis
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supporting information; body text
p. 4163 - 4165
(2010/09/12)
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- USE OF THE IRRITATING PRINCIPAL OLEOCANTHAL IN OLIVE OIL, AS WELL AS STRUCTURALLY AND FUNCTIONALLY SIMILAR COMPOUNDS
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The invention provides methods of synthesizing the purified enantiomers of oleocanthal. The invention further provides methods of using oleocanthals in various formulations including, food additives; pharmaceuticals; cosmetics; animal repellants; and discovery tools for mammalian irritation receptor genes, gene products, alleles, splice variants, alternate transcripts and the like.
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Page/Page column 15-16
(2009/04/24)
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- Synthesis of (4S,5S)-4,5-O-isopropylidene-cyclopent-2-ene-1-one via the intramolecular Reformatsky reaction
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Isomeric mixtures of bromo- and iodohydrins produced via bromohydroxylation and iodohydroxylation of exo-methylene derivative 2 undergo an intramolecular aldol cyclization-dehydration sequence under Reformatsky reaction conditions to give cyclopentenone 1
- Ivanova, Nadezhda A.,Valiullina, Zuleykha R.,Akhmetdinova, Natal'ya P.,Miftakhov, Mansur S.
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experimental part
p. 6179 - 6181
(2009/04/04)
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- Traceless solid-phase synthesis of hydroxylated cyclopentenones
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Intramolecular nitrone-alkene cycloadditions on solid phase can be performed using polymer-bound hydroxylamine. Condensation of this reagent with sugar derived 4-pentenals followed by N-O cleavage, quaternization of the amine thus produced, and finally oxidative elimination of the amino group detaches the chiral hydroxylated cyclopentenones from the polymer. The natural antibiotic pentenomycin I was prepared in this way.
- Stathakis, Christos I.,Gallos, John K.
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body text
p. 6804 - 6806
(2009/04/07)
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- Syntheses of (-)-oleocanthal, a natural NSAID found in extra virgin olive oil, the (-)-deacetoxy-oleuropein aglycone, and related analogues
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(Chemical Equation Presented) Phenolic compounds extracted from extra virgin olive oil have attracted considerable recent attention. One of the components, (-)-oleocanthal (1), an inhibitor of the COX-1 and COX-2 enzymes, possesses similar potency as the NSAID ibuprofen. In this, a full account, we disclose the first- and now second-generation syntheses of both enantiomers of the oleocanthals, as well as the first synthesis of the closely related (-)-deacetoxy-oleuropein aglycone and a series of related analogues for structure activity studies. To demonstrate the utility of the second-generation synthesis, multigram quantities of (-)-oleocanthal were prepared in 10 steps (14% overall yield) from commercially available D-lyxose.
- Smith III, Amos B.,Sperry, Jeffrey B.,Han, Qiang
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p. 6891 - 6900
(2008/02/11)
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- Synthesis and assignment of absolute configuration of (-)-oleocanthal: A potent, naturally occurring non-steroidal anti-inflammatory and anti-oxidant agent derived from extra virgin olive oils
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(Chemical Equation Presented) Effective total syntheses and the assignment of absolute configurations of both the (+)- and (-)-enantiomers of oleocanthal 1 (a.k.a. deacetoxy ligstroside aglycon), the latter derived from extra virgin olive oils and known to be responsible for the back of the throat irritant properties of olive oils, have been achieved. The absolute and relative stereochemistry of the naturally occurring enantiomer (-)-1 proved to be 3S,4E. Both syntheses begin with D-(-)-ribose, proceed in 12 steps, and are achieved with an overall yield of 7%. Both enantiomers proved to be non-steroidal anti-inflammatory and anti-oxidant agents.
- Smith III, Amos B.,Han, Qiang,Breslin, Paul A. S.,Beauchamp, Gary K.
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p. 5075 - 5078
(2007/10/03)
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- An improved approach to chiral cyclopentenone building blocks. Total synthesis of pentenomycin I and neplanocin A
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An improved approach to enantiomerically pure hydroxylated cyclopentenones is reported here, which involves intramolecular nitrone cycloaddition of sugar-derived chiral pent-4-enals and hex-5-en-ones-2 followed by N-O bond cleavage, quaternization of the amine thus produced, and finally oxidative elimination of the amino group. Synthesis of pentenomycin I and neplanocin A is described following this methodology.
- Gallos, John K.,Stathakis, Christos I.,Kotoulas, Stefanos S.,Koumbis, Alexandros E.
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p. 6884 - 6890
(2007/10/03)
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- Practical Synthesis of D- and L-2-Cyclopentenone and their Utility for the Synthesis of Carbocyclic Antiviral Nucleosides against Orthopox Viruses (Smallpox, Monkeypox, and Cowpox Virus)
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Highly efficient and practical methodology for the syntheses of D- and L-4,5-O-isopropylidene-2-cyclopentenone (9 and 22), versatile intermediates for the synthesis of carbocyclic nucleosides, have been developed via a ring-closing metathesis reaction from D-ribose in eight steps. The utility of D- and L-4,5-O-isopropylidene-2-cyclopentenone is demonstrated by their application for the preparation of D-cyclopentyl-6-azauridine 12 and D-cyclopentenyl-5-halocytosine nucleosides (33-35) using Mitsunobu reaction to introduce pyrimidine bases as potential antiviral agents. Preliminary antiviral activity against orthopox viruses (smallpox, monkeypox, and cowpox virus) of the synthesized nucleosides are described.
- Jin, Yun H.,Liu, Peng,Wang, Jianing,Baker, Robert,Huggins, John,Chu, Chung K.
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p. 9012 - 9018
(2007/10/03)
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- Chiral preparation of polyoxygenated cyclopentanoids
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A series of polyoxygenated cyclopentanoids, including 2,2-dimethyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-one, has been prepared in both enantiomeric forms from cyclopentadiene by employing lipase-mediated kinetic resolution as the key step. Thus, cyclopentadiene is first transformed into racemic cis-4-cumyloxycyclopent-2-en-1-ol which is resolved under transesterification conditions in the presence of lipase PS. After transformation into the corresponding tert-butyldimethylsilyl (TBS) ethers, each of the enantiomers is cis-dihydroxylated diastereoselectively from the less hindered face which is transformed into the 2,3-O-isopropylidene-1,4-di- O-protected (trans-1,2:cis-2,3:trans-3,4)-1,2,3,4-cyclopentanetetraol. Selective removal of the 1,4-protecting group gives the corresponding 2,3,4- O-protected cyclopentanols which are further transformed into the 2,3,4-O- protected cyclopentanones on oxidation without suffering β-elimination. Exposure of the cyclopentanones to warm acetic acid allows β-elimination to give rise to the dehydration product 2,2,-dimethyl-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-4-one having the corresponding chirality without losing their original chiral integrity.
- Nakashima, Hiromi,Sato, Masayuki,Taniguchi, Takahiko,Ogasawara, Kunio
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p. 817 - 823
(2007/10/03)
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- Concise synthesis of (4S,5S)-4,5-(isopropylidenedioxy)-2-cyclopentenone and a novel C2-symmetric ketone
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A new and concise synthesis of the useful synthetic intermediate 1 is described which also allows access to a novel C2-symmetric ketone 2. The route relies on the Sharpless asymmetric dihydroxylation of fulvenes.
- Armstrong, Alan,Hayter, Barry R.
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p. 1677 - 1684
(2007/10/03)
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- Chemoenzymatic synthesis of a versatile cyclopentenone: (+)-(3aS,6aS)-2,2-dimethyl-3aβ,6aβ-dihydro-4H-cyclopenta-1,3-dioxol- 4-one
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The title cyclopentenone has been prepared by enzymatic resolution of cis-4-phenyloxy- and cis-4-(4-methoxyphenyloxy)-cyclopent-2-en-1-ol in isopropenyl acetate using Pseudomonas cepacia lipase. The use of a 4-methoxyphenyloxy-alcohol intermediate enabled the use of both enzymatically resolved enantiomers in the synthesis of the desired (+)-enone.
- Biadatti, Thibaud,Esker, John L.,Johnson, Carl R.
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p. 2313 - 2320
(2007/10/03)
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- 4-Hydroxycyclopent-2-en-1-one and derivatives as chiral synthetic equivalents of cyclopentadienone in asymmetric Diels-Alder reactions
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Endo-tricyclodecadienone 8a and related annelated-cyclopentenones (8b, 20, 21a-c and 22) are synthesized in good chemical yield by a Diels-Alder reaction of 4-hydroxycyclo-pent-2-en-1-one 12a and derivatives 12b-h with an appropriate diene. These additions are considerably accelerated by Lewis catalysts, high pressure and by using water as solvent. Due to opposing steric and electronic effects the diastereofacial selectivity of the asymmetric cycloadditions is moderate. By carefully choosing the substrate and reaction conditions an acceptable π-facial selectivity can be achieved.
- Dols,Klunder,Zwanenburg
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p. 8515 - 8538
(2007/10/02)
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- Chemoenzymatic Synthesis of 4-Substituted Riboses. S-(4'-Methyladenosyl)-L-homocysteine
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The synthesis of 4-C-methyl-D-ribose, 4-C-phenyl-D-ribose, D-ribose-4-d, and L-ribose derivatives as well as the title nucleoside by a chemoenzymatic strategy beginning from cyclopentadiene is described.
- Johnson, Carl R.,Esker, John L.,Zandt, Michael C. Van
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p. 5854 - 5855
(2007/10/02)
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- HOMOCHIRAL KETALS IN ORGANIC SYNTHESIS. ENANTIOSELECTIVE SYNTHESIS OF (4S,5S)-4,5-DIHYDROXYCYCLOPENT-2-EN-1-ONE ISOPROPYLIDINE KETAL
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The title compound has been synthesized in 17percent yield over six step from 2-cyclopenten-1-one.The key step is catalytic osmylation of 4-bromo-2-cyclopenten-1-one 1,4-di-O-benzyl-D-threitol ketal to produce a chromatographically separable mixture of diastereomeric diols.
- Flann, Christopher J.,Mash, Eugene A.
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p. 391 - 402
(2007/10/02)
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- CARBOCYCLES FROM CARBOHYDRATES: A SIMPLE ROUTE TO AN ENANTIOMERICALLY PURE PROSTAGLANDIN INTERMEDIATE
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The enone 7, the key intermediate in the three component coupling approach to prostaglandins, has been prepared efficiently from commercially available D-ribonic acid γ-lactone by an intramolecular aldol condensation.
- Belanger, Pascale,Prasit, Petpiboon
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p. 5521 - 5524
(2007/10/02)
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