Startseite A concise and efficient synthesis of (+)-preussin
Artikel Open Access

A concise and efficient synthesis of (+)-preussin

  • Enzo B. Arévalo-García EMAIL logo
Veröffentlicht/Copyright: 3. Februar 2014
Artikel downloaden (PDF)
Heterocyclic Communications
Aus der Zeitschrift Heterocyclic Communications Band 20 Heft 1

Abstract

A novel and efficient synthesis of (+)-preussin (7) starting from N-butoxycarbonyl-L-phenylalaninal (1) is described. This natural product was synthesized under mild conditions and with good overall yield.

Keywords: cyclization; phenylalanine; pyrrolidines; vinylation

Introduction

The pyrrolidine ring is a significant motif found in many natural and unnatural bioactive molecules. It occurs in a range of pheromones, alkaloids, drug candidates, and other important compounds [1–4] that are antibacterial and neuroexcitatory agents, venoms, or fungicides [5–9]. Consequently, molecules which possess the pyrrolidine motif are often promising drug candidates for use in the pharmaceutical industry, and enantomerically pure pyrrolidines are excellent chiral building blocks in asymmetric synthesis [8, 10–13]. Accordingly, there is continuous research towards the stereocontrolled access to functionalized pyrrolidines. One of those important compounds is preussin (structure 7 in Scheme 1).

Scheme 1 Synthesis of (+)-preussin (7).
Scheme 1

Synthesis of (+)-preussin (7).

Compound 7 is a naturally occurring pyrrolidine alkaloid isolated from the fermentation of Aspergillus ochraceus [14, 15]. It has been shown to possess a potent antifungal activity [16]. Its interesting structural features and remarkable biological activity have made preussin an attractive target for synthetic chemists, and several approaches to the preparation of 7 have been reported [17–33]. To demonstrate the synthetic utility of the methodology of Arévalo-García and Colmenares [34], the details of a novel synthetic process leading to the preparation of this natural product, (2S,3S,5R)-(+)-preussin (7) are communicated here.

Results and discussion

From the retrosynthetic analysis (not shown), it was clear that the target compound 7 could be acquired from the readily available precursor 1 [35] (Scheme 1). Thus, the synthesis of 7 started with the reaction of aldehyde 1 (1 eq.) in THF with vinylmagnesium bromide (4 eq.) at 0°C affording a syn-amino alcohol [36, 37] as the major product (syn:anti=94:6) in 76% yield. Protection of the hydroxy group of this adduct (1 eq.) with tert-butyldimethylsilyl chloride (2.2 eq.) in pyridine afforded protected alcohol 2 [38] in 90% overall yield. Hydroboration of 2 with 9-borabicyclo[3.3.1]nonane (1.4 eq.) in the presence of hydrogen peroxide and sodium hydroxide at room temperature afforded alcohol 3 in 81% yield [38]. Next, the primary hydroxyl group in 3 was activated by the reaction with MeSO2Cl (2.9 eq.) in the presence of Et3N in dichloromethane. This reaction proceeded smoothly and was followed by an intramolecular SN2 displacement affording the cyclized product 4 in 71% yield. Following Beak’s methodology [39–42], lithiation of 4 with s-BuLi (1.3 eq.) in the presence of TMEDA followed by the reaction of the resultant 2-lithiopyrrolidine with N,N,-dimethylformamide (1.5 eq.) provided a mixture of aldehydes (cis:trans=93:7) from which the major product 5 was obtained in 78% yield by flash chromatography. Treatment of aldehyde 5 with the Wittig reagent generated in situ from n-octyltriphenylphosphonium iodide (1.5 eq.) and n-butyllithium (1.6 eq.) afforded an olefin (83%), which was rapidly hydrogenated (1 atm. H2, 10% Pd/C, rt, EtOH) obtaining 6 [43] in quantitative yield. The end-game was accomplished through the one-pot reported procedure, leading to the deprotection/reduction (LiAlH4/NaOH) [44] of 6, completing the synthesis of (+)-preussin (7), in 91% yield (Scheme 1). Its 1H NMR and 13C NMR spectra are virtually identical to literature data [14, 15, 24, 26, 27, 29]. Its specific optical rotation (c 1.1, CHCl3) that is greater than the literature value (c 1.0, CHCl3) demonstrates that product 7 of high optical purity was obtained. The high chemical purity is strongly supported by the excellent results of elemental analysis.

Conclusions

A new efficient, stereoselective route to biologically important (+)-preussin was developed. The strategy can be extended to the synthesis of other members of this class of biologically active products, and further studies in this field are currently underway.

Experimental

Solvents and all other reagents were obtained from Aldrich, Fluka or Avocado. Solvents were dried using common laboratory methods [45], and their evaporation was performed in a rotary evaporator under reduced pressure. Analytical thin-layer chromatography (TLC) was performed on a pre-coated Merck silica-gel 60 F254 TLC plate. Purification was performed by flash column chromatography [46] on silica gel (Kieselgel-60, Merck, 230–400 mesh). The NMR spectra were recorded with a Bruker Avance spectrometer in CDCl3 at 300 MHz (1H NMR) and 75 MHz (13C NMR). The IR spectra were recorded on a Jasco FT/IR-430 spectrophotometer. Yields refer to chromatographically and spectroscopically pure compounds.

(2S,3S)-1-(tert-Butoxycarbonyl)-3-tert-butyldimethylsiloxy-2-(phenylmethyl)pyrrolidine (4)

A solution of alcohol 3 [38] (900 mg, 2.19 mmol) and Et3N (0.88 mL, 6.35 mmol) in dichloromethane (5 mL) at -5°C was treated with MeSO2Cl (0.49 mL, 6.35 mmol). The mixture was stirred at -5°C to 0°C for 20 min and then warmed to ambient temperature. Stirring was continued for another 1 h and then the mixture was quenched by addition of saturated NH4Cl (6 mL) and H2O (3 mL). The aqueous layer was extracted with dichloromethane (3×10 mL), and the extract was washed with brine and dried over anhydrous Na2SO4. The solvent was then removed under reduced pressure and the product was purified by flash column chromatography eluting with 10% EtOAc in petroleum ether to afford 4 (610 mg, 71%) as a colorless oil; 1H NMR: δ 7.08 (m, 5H), 4.10 (dt, J = 7.0 Hz and 7.0 Hz, 1H), 4.0 (dt, J = 6.1 Hz and 6.0 Hz, 1H), 3.68 (m, 2H), 3.01 (m, 2H), 1.95 (m, 2H), 1.35 (s, 9H), 0.88 (s, 9H), 0.08 (s, 3H), 0.06 (s, 3H); 13C NMR: δ 154.9, 139.5, 129.6, 128.3, 126.0, 79.5, 71.0, 61.9, 43.4, 34.5, 31.3, 28.4; 20.1, -5.0, -5.1; IR (film): 1720, 1600, 1405, 1352, 1255, 837 cm-1. Anal. Calcd for C22H37NO3Si: C, 67.47; H, 9.52; N, 3.58. Found: C, 67.39; H, 9.51; N, 3.61.

(2S,4S,5S)-1-(tert-Butoxycarbonyl)-4-tert-butyldimethylsiloxy-5-(phenylmethyl)pyrrolidine-2-carbaldehyde (5)

To a stirred solution of 4 (0.962 g, 2.45 mmol) in ether (10 mL) under nitrogen atmosphere was added TMEDA (0.482 mL, 3.19 mmol). The solution was cooled to -65°C and s-BuLi (1.38 M in cyclohexane, 2.46 mL, 3.19 mmol) was added dropwise. The solution was allowed to warm to -30°C and was stirred for another 30 min. It was then cooled to -78°C and treated with DMF (0.284 mL, 3.68 mmol). After 10 min the mixture was quenched with saturated NH4Cl (3 mL), allowed to warm to room temperature, and diluted with ether (30 mL). The aqueous layer was extracted with ether (3×6 mL) and the combined ether solutions were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was chromatographed on silica gel (hexane/ethyl acetate, 90:10) to afford 0.803 g (78%), (diastereoselectivity, 93:7) of 5, as a colorless oil; 1H NMR: δ 9.25 (br s, 1H), 7.15 (m, 5H), 4.18 (dt, J = 6.1 Hz and 7.2 Hz, 1H), 4.09 (m, 1H), 3.85 (dt, J = 2.0 Hz and 7.4 Hz, 1H), 2.90 (m, 2H), 2.1 (m, 2H), 1.44 (s, 9H), 0.90 (s, 9H), 0.05 (s, 3H), -0.04 (s, 3H); 13C NMR: δ 201.0, 156.6, 139.0, 136.0, 129.0, 128.2, 71.0, 68.0, 61.0, 60.3, 33.3, 27.0, 26.1, 21.3, 18.3, -4.0; IR (film): 2730, 1730, 1705, 1570, 815 cm-1. Anal. Calcd for C23H37NO4Si: C, 65.83; H, 8.89; N, 3.34. Found: C, 65.79; H, 8.85; N, 3.43.

(2S,3S,5R)-(+)-Preussin (7)

A solution of 6 (500 mg, 0.97 mmol) in THF (5 mL) was stirred at 0°C under nitrogen atmosphere and treated dropwise using a syringe with a solution of LiAlH4 (5.85 mL, 5.85 mmol, 1 M in THF). The resulting mixture was heated under reflux until the starting material was consumed as determined by TLC analysis (approx. 10 h). The reaction mixture was then cooled to 0°C, quenched with water (2 mL), and diluted with diethyl ether (10 mL). Aqueous NaOH (5 mL, 10 M) and water (1 mL) were then added and an insoluble white precipitate was formed. The organic supernatant was decanted to an Erlenmeyer flask and the precipitate was washed with diethyl ether. The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The oily residue was subjected to flash chromatography eluting with hexane/ethyl acetate, 5:1, to afford 280.2 mg (91%) of (+)-preussin as a colorless oil; 1H NMR: δ 7.21 (m, 5 H), 3.5 (m, 1 H), 2.86 (m, 2 H), 2.3 (s, 3H), 2.23 (m, 1H), 1.69 (m, 1 H), 1.46 (m, 1 H), 2.66–2.60 (m, 2 H), 1.30–1.18 (m, 16 H), 0.88 (t, J = 7.0 Hz, 3H); 13C NMR: δ 138.5, 129.2, 128.4, 126.0, 71.5, 68.7, 53.4, 38.6, 35.0, 33.5, 31.8, 29.9, 29.5, 29.3, 29.0, 26.3, 22.7, 14.1; IR (film): 3400, 2935, 2900, 1457, 1400, 1170 cm-l. Anal. Calcd for C21H35NO: C, 79.4; H, 11.1; N, 4.41. Found: C, 79.1; H, 10.9; N, 4.39.

Corresponding author: Enzo B. Arévalo-García, Educational Research Institute, Górczewska 8, Warsaw, 01–180, Poland; and EARTH University, P.O. Box 4442-1000, San José, Costa Rica, e-mail:

The author is grateful to Mrs Agnieszka Chilicka for proofreading this paper and to EARTH University and the Educational Research Institute for partial support of this work.

References

[1] Hanessian, S.; Bayrakdarian, M.; Luo, X. Total synthesis of A-315675: a potent inhibitor of influenza neuraminidase. J. Am. Chem. Soc. 2002, 124, 4716–4721; Erratum: J. Am. Chem. Soc. 2003, 125, 4958.Suche in Google Scholar

[2] Ma, D.; Yang, J. Total synthesis of kaitocephalin, the first naturally occurring AMPA/KA receptor antagonist. J. Am. Chem. Soc. 2001, 123, 9706–9707.Suche in Google Scholar

[3] Michael, J. P. Indolizidine and quinolizidine alkaloids. Nat. Prod. Rep. 2005, 22, 603–626.Suche in Google Scholar

[4] Watanabe, H.; Okue, M.; Kobayashi, H.; Kitahara, T. The first synthesis of kaitocephalin based on the structure revision. Tetrahedron Lett. 2002, 43, 861–864.Suche in Google Scholar

[5] Attygalle, A. B.; Morgan, D. E. Chemicals from the glands of ants. Chem. Soc. Rev. 1984, 13, 245–278.Suche in Google Scholar

[6] Flanagan, D. M.; Jouilli, M. M. Synthetic strategies for the construction of 3-pyrrolidinol, a versatile nitrogen. Heterocycles 1987, 26, 2247–2265.Suche in Google Scholar

[7] Maesiot, G.; Delaude, C. In The Alkaloids; Brosei, A., Ed.; Academic Press: New York, 1986; Vol. 27, Chapter 3. Pyrrolidine Alkaloids, pp. 269–322.10.1016/S0099-9598(08)60309-0Suche in Google Scholar

[8] Numata, A.; Ibuka, T. In The Alkaloids; Broesi, A., Ed.; Academic Press: New York, 1987; Vol. 31, Chapter 6. Alkaloids from Ants and Other Insects, pp. 193–315.10.1016/S0099-9598(08)60261-8Suche in Google Scholar

[9] Pedder, D. J.; Fales, H. M.; Jaouni, T.; Blum, M.; MacConnell, J.; Crewe, R. M. Constituents of the venom of a South African fire ant (Solenopsis punctaticeps): 2,5 dialkylpyrrolidines and -pyrrolines, identification and synthesis. Tetrahedron1976, 32, 2275–2279.Suche in Google Scholar

[10] O’Hagan, D. Pyrrole, pyrrolidine, pyridine, piperidine and tropane alkaloids. Nat. Prod. Rep. 2000, 17, 435–446.Suche in Google Scholar

[11] Hanessian, S.; Yun, H.; Tintelnot-Blomley, M. Stereoselective synthesis of constrained azacyclic hydroxyethylene isosteres as aspartic protease inhibitors: dipolar cycloaddition and related methodologies toward branched pyrrolidine and pyrrolidinone carboxylic acids. J. Org. Chem. 2005, 70, 6746–6756.Suche in Google Scholar

[12] Huryn, D. M. In Comprehension Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991, Vol. 1, pp 64–71.Suche in Google Scholar

[13] Schomaker, J. M.; Bhattacherjee, J. Y.; Borhan, B. Diastereomerically and enantiomerically pure 2,3-disubstituted pyrrolidines from 2,3-aziridin-1-ols using a sulfoxonium ylide: a one-carbon homologative relay ring expansion. J. Am. Chem. Soc. 2007, 129, 1996–2003 (and references cited therein).Suche in Google Scholar

[14] Johnson, J. H.; Phillipson, D. W.; Khale, A. D. The relative and absolute stereochemistry of the antifungal agent preussin. J. Antibiot. 1989, 42, 1184–1185.Suche in Google Scholar

[15] Schwarts, R. E.; Liesc, J.; Hensens, O.; Zitano, L.; Honeycutt, S.; Garrity, G.; Fromtling, R. A.; Onishi, J.; Monaghan, R. L-657,398, A novel antifungal agent: fermentation, isolation, structural elucidation and biological properties. J. Antibiot. 1988, 41, 1774–1779.Suche in Google Scholar

[16] Canova, S.; Bellosta, V.; Cossy, J. Total synthesis of (+)-preussin: control of the stereogenic centers by enantioselective allyltitanations. Synlett2004, 10, 1811–1813.Suche in Google Scholar

[17] Armas, P. D.; Tellado-Garcia, F.; Tellado-Marrero, J. J.; Robles, J. Diastereoselective formal synthesis of the antifungal agent, (+)-preussin. A new entry to chiral pyrrolidines. Tetrahedron Lett.1998, 39, 131–134.Suche in Google Scholar

[18] Bach, T.; Brummerhop, H. Unprecedented facial diastereoselectivity in the Paternò-Büchi reaction of a chiral dihydropyrrole – a short total synthesis of (+)-preussin. Angew. Chem. Int. Ed.1998, 37, 3400–3402.Suche in Google Scholar

[19] Davis, F. A.; Deng, J. Asymmetric synthesis of (+)-preussin from N-sulfinyl δ-amino β-ketoesters. Tetrahedron2004, 60, 5111–5115.Suche in Google Scholar

[20] Deng, W.; Overman, L. E. Enantioselective total synthesis of either enantiomer of the antifungal antibiotic preussin (L-657,398) from (S)-phenylalanine. J. Am. Chem. Soc. 1994, 116, 11241–11250.Suche in Google Scholar

[21] Kadota, I.; Saya, S.; Yamamoto, Y. Novel route to the synthesis of hydroxylated pyrrolidine derivatives via the intramolecular reaction of γ-aminoallylstannane with aldehyde. Total synthesis of (+)-preussin. Heterocycles1997, 46, 335–348.Suche in Google Scholar

[22] Kanazawa, A.; Gillet, S.; Delair, P.; Greene, A. E. Practical asymmetric approach to pyrrolidinones: efficient synthesis of (+)-preussin and (–)-AHPPA. J. Org. Chem.1998, 63, 4660–4663.Suche in Google Scholar

[23] Krasinski, A.; Gruza, H.; Jurczak, J. Efficient stereoselective synthesis of (2S,3S,5R)-(+)-preussin. Heterocycles2001, 54, 581–584.Suche in Google Scholar

[24] Lee, K.-Y.; Kim, Y.-H.; Oh, C.-Y.; Ham, W.-H. Facile and efficient total synthesis of (+)-preussin. Org. Lett.2000, 2, 4041–4042.Suche in Google Scholar

[25] McGrane, P. L.; Livinghouse, T. Synthetic applications of imidotitanium-alkyne [2+2] cycloadditions. A concise, stereocontrolled total synthesis of the antifungal agent (+)-preussin. J. Am. Chem. Soc. 1993, 115, 11485–11489.Suche in Google Scholar

[26] Okue, M.; Watanabe, H.; Kitahara, T. A concise synthesis of (+)-preussin. Tetrahedron2001, 57, 4107–4110.Suche in Google Scholar

[27] Overhand, M.; Hecht, S. M. A concise synthesis of the antifungal agent (+)-preussin. J. Org. Chem. 1994, 59, 4721–4722.Suche in Google Scholar

[28] Pak, C. S.; Lee, G. H. Total synthesis of (+)-preussin, a novel antifungal agent. J. Org. Chem. 1991, 56, 1128–1133.Suche in Google Scholar

[29] Raghavan, S.; Rasheed, M. A. A novel and stereospecific synthesis of (+)-preussin. Tetrahedron2003, 59, 10307–10312.10.1016/j.tet.2003.10.032Suche in Google Scholar

[30] Schaumann, E.; Beier, C. An epoxide-based enantioselective synthesis of the antifungal antibiotic (+)-preussin. Synthesis1997, 11, 1296–1300.10.1055/s-1997-1347Suche in Google Scholar

[31] Shimazaki, M.; Okazaki, F.; Nakajima, F.; Ishikawa, T.; Ohta, A. Synthesis of (+)-preussin. Heterocycles1993, 36, 1823–1836.Suche in Google Scholar

[32] Verma, R.; Ghosh, S. K. A silicon controlled total synthesis of the antifungal agent (+)-preussin. Chem. Commun. 1997, 17, 1601–1602.Suche in Google Scholar

[33] Yoda, H.; Yamazaki, H.; Takabe, K. A novel stereoselective synthesis of enantiomerically pure antifungal agent, (+)-preussin. Tetrahedron Asymm.1996, 7, 373–374.Suche in Google Scholar

[34] Arévalo-García, E. B.; Colmenares, J. C. A versatile synthesis of (+) deoxoprosopinine and (–) deoxoprosophylline. Tetrahedron Lett. 2008, 49, 6972–6973.Suche in Google Scholar

[35] Alfaro, R.; Yuste, F.; Ortiz, B.; Sánchez-Obregón, R.; Ruano, J. L. G. γ-Amino vinyl sulfoxides in asymmetric synthesis. Synthesis of optically pure α-substituted β-amino nitriles. Tetrahedron2009, 65, 357–363.Suche in Google Scholar

[36] Datta, A.; Veeresa, G. A stereoselective route to hydroxyethylamine dipeptide isosteres. J. Org. Chem.2000, 65, 7609–7611.Suche in Google Scholar

[37] Spaltenstein, A.; Leban, J. J.; Huang, J. J.; Reinhardt, K. R.; Viveros, O. H.; Sigafoos, J.; Crouch, R. Design and synthesis of novel protease inhibitors. Tripeptide α′,β′-epoxyketones as nanomolar inactivators of the proteasome. Tetrahedron Lett. 1996, 37, 1343–1346.Suche in Google Scholar

[38] Pais, G. C. G.; Maier, E. M. Efficient synthesis of the γ-amino-β-hydroxy acid subunit of hapalosin. J. Org. Chem.1999, 64, 4551–4554.Suche in Google Scholar

[39] Beak, P.; Basu, A.; Gallagher, D. J.; Park, Y. S.; Thayumanavan, S. Regioselective, diastereoselective, and enantioselective lithiation-substitution sequences: reaction pathways and synthetic applications. Acc. Chem. Res. 1996, 29, 552–560.Suche in Google Scholar

[40] Beak, P.; Lee, W. K. α-Lithioamine synthetic equivalents: syntheses of diastereoisomers from the Boc-piperidines. J. Org. Chem. 1990, 55, 2578–2580.Suche in Google Scholar

[41] Beak, P.; Lee, W. K. α-Lithioamine synthetic equivalents: syntheses of diastereoisomers from Boc derivatives of cyclic amines. J. Org. Chem. 1993, 58, 1109–1117.Suche in Google Scholar

[42] Wilkinson, T. J.; Stehle, N. W.; Beak, P. Enantioselective syntheses of 2-alkyl- and 2,6-dialkylpiperidine alkaloids: preparations of the hydrochlorides of (–)-coniine, (–)-solenopsin A, and (–)-dihydropinidine. Org. Lett.2000, 2, 155–158.Suche in Google Scholar

[43] Huang, P. Q.; Wu, T. J.; Ruan, Y. P. A flexible approach to (S)-5-alkyl tetramic acid derivatives: application to the asymmetric synthesis of (+)-preussin and protected (3S,4S)-AHPPA. Org. Lett.2003, 5, 4341–4344.Suche in Google Scholar

[44] Beaudoin, M.; Wolfe, J. P. A concise stereoselective synthesis of preussin, 3-epi-preussin and analogues. Org. Lett.2006, 8, 2353–2356.Suche in Google Scholar

[45] Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory Chemicals, 4th ed.; Butterworth-Heinemann: Oxford, 1996.Suche in Google Scholar

[46] Still, W. C.; Kahn, M.; Mitra, A. Rapid chromatographic techniques for preparative separation with moderate resolution. J. Org. Chem.1978, 43, 2923–2925.Suche in Google Scholar

Received: 2013-12-12
Accepted: 2014-1-9
Published Online: 2014-02-03
Published in Print: 2014-02-01

©2014 by Walter de Gruyter Berlin Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Artikel in diesem Heft

  2. Frontmatter
  3. Preliminary Communication
  4. One-pot three-component synthesis of substituted 2-(1,2,3-triazol-1-yl)pyrimidines from pyrimidin-2-yl sulfonates, sodium azide and active methylene ketones
  5. Research Articles
  6. A convenient synthesis of 5,5′-bi-1,2,4-triazines via direct S-arylation and its application in the synthesis of 2,2′-bipyridines
  7. An efficient approach to the key intermediate of rosuvastatin
  8. Synthesis and properties of multifunctional hindered amine light stabilizers
  9. Tertiary formylated amines by microwave irradiation of N,N-dimethyl-N′-(2-pyridyl)formamidines with methyl vinyl ketone
  10. Synthesis and antimicrobial activity of some novel 2-thienyl substituted heterocycles
  11. Synthesis of 2-amino-5-mercapto-1,3,4-thiadiazole derivatives
  12. An easy and efficient protocol for the condensation reaction of isatin and N-substituted isatins with 1,2-diaminobenzene using low cost reusable clay catalyst
  13. Synthesis and antimicrobial activities of novel 6-(1,3-thiazol-4-yl)-1,3-benzoxazol-2(3H)-one derivatives
  14. A concise and efficient synthesis of (+)-preussin
  15. Synthesis, X-ray structural characterization, NLO, MEP, NBO and HOMO-LUMO analysis using DFT study of Zn(II)bis(3,4 dimethoxybenzoate)bis(nicotinamide) dihydrate
https://doi.org/10.1515/hc-2013-0236
Schlagwörter für diesen Artikel
cyclization; phenylalanine; pyrrolidines; vinylation
Creative Commons
BY-NC-ND 3.0

Artikel in diesem Heft

  2. Frontmatter
  3. Preliminary Communication
  4. One-pot three-component synthesis of substituted 2-(1,2,3-triazol-1-yl)pyrimidines from pyrimidin-2-yl sulfonates, sodium azide and active methylene ketones
  5. Research Articles
  6. A convenient synthesis of 5,5′-bi-1,2,4-triazines via direct S-arylation and its application in the synthesis of 2,2′-bipyridines
  7. An efficient approach to the key intermediate of rosuvastatin
  8. Synthesis and properties of multifunctional hindered amine light stabilizers
  9. Tertiary formylated amines by microwave irradiation of N,N-dimethyl-N′-(2-pyridyl)formamidines with methyl vinyl ketone
  10. Synthesis and antimicrobial activity of some novel 2-thienyl substituted heterocycles
  11. Synthesis of 2-amino-5-mercapto-1,3,4-thiadiazole derivatives
  12. An easy and efficient protocol for the condensation reaction of isatin and N-substituted isatins with 1,2-diaminobenzene using low cost reusable clay catalyst
  13. Synthesis and antimicrobial activities of novel 6-(1,3-thiazol-4-yl)-1,3-benzoxazol-2(3H)-one derivatives
  14. A concise and efficient synthesis of (+)-preussin
  15. Synthesis, X-ray structural characterization, NLO, MEP, NBO and HOMO-LUMO analysis using DFT study of Zn(II)bis(3,4 dimethoxybenzoate)bis(nicotinamide) dihydrate
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 29.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hc-2013-0236/html
Button zum nach oben scrollen