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(–)-5-[(4R,5R)-5-(Benzyloxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-4,7-dihydro-1,3-dioxepine

1
INTEQUI-CONICET-Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, 5700 San Luis, Argentina
2
Instituto Universitario de Bio-Orgánica “Antonio González”, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez, 2, 38206 La Laguna, Tenerife, Spain
3
Institut für Organische Chemie, Universität Regensburg, Universitätsstr. 31, 93040 Regensburg, Germany
4
ICMA, CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
*
Authors to whom correspondence should be addressed.
Molbank 2010, 2010(2), M680; https://doi.org/10.3390/M680
Submission received: 11 March 2010 / Accepted: 30 April 2010 / Published: 30 April 2010

Abstract

:
The synthesis of (−)-5-[(4R,5R)-5-(benzyloxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-4,7-dihydro-1,3-dioxepine is reported. Product character-ization was carried out by IR, 1H NMR, 13C NMR, MS, elemental analysis and optical rotation.

Graphical Abstract

Acetals are frequently used as protecting groups for carbonyl groups in organic synthesis mainly due to their stability towards hydrolysis by bases [1]. As well as being remarkable synthetic building blocks, cyclic acetals are also important in nature. For instance, the most stable form of glucose in solution is its cyclic hemiacetal, maltose is an acetal made from two glucose units, and acetaldehyde diethyl acetal is an important flavouring compound in distilled beverages [2]. Pharmaceutical industry has also commercialized a number of bioactive acetonide-containing bioactive products such as fluocinolone acetonide or triamcinolone acetonide, which are potent corticosteroids primarily used in dermatology to reduce skin inflammation [3].
Herein, we report the synthesis of (−)-5-[(4R,5R)-5-(benzyloxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-4,7-dihydro-1,3-dioxepine (2) by refluxing the corresponding allylic diol 1 in acetone for 24 h (Scheme 1). Chiral precursor 1 was prepared by reduction of the appropriate butenolide as reported previously [4].

Experimental

General

1H and 13C NMR spectra were recorded at 25 °C on a Bruker Avance 500 spectrometer in CDCl3 as solvent, and chemical shifts are reported relative to Me4Si (δ = 0). Low- and high-resolution mass spectra were obtained by using a Micromass VG Autospec spectrometer. Elemental analysis was performed on a Fisons Instrument EA 1108 CHNS-O analyzer. Infrared spectra were recorded on a Bruker IFS 55 spectrophotometer on compounds dispersed on a NaCl disc. Optical rotations were determined for solutions in chloroform with a Perkin Elmer 343 polarimeter using a sodium lamp (589 nm). Thin-layer chromatography was carried out on Merck aluminium sheets coated with silica gel 60 F254. Compounds were visualized by use of 254 nm UV light and/or phosphomolybdic acid 20 wt.% solution in ethanol with heating. All solvents were purified by standard techniques [5]. Flash chromatography was performed on Merck silica gel 60 (0.040−0.063 mm, 230−400 mesh ASTM). Anhydrous magnesium sulfate was used for drying solutions.
Synthesis of (−)-5-[(4R,5R)-5-(benzyloxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-4,7-dihydro-1,3-dioxepine (2): To a stirred solution of allylic diol 1 (308 mg, 1.0 mmol) in acetone (25 mL), p-toluenesulfonic acid (p-TsOH) (3 mg, 0.017 mmol) was added at room temperature. The reaction mixture was refluxed for 24 h, until the TLC analysis showed that no starting material was present. The solvent was concentrated and the residue diluted with Et2O (30 mL) and washed with a 5% solution of NaHCO3. The combined organic phases were dried (MgSO4), filtered, concentrated, and the residue purified by silica gel column chromatography, eluting with AcOEt:n-hexane 10:90. Product 2 (303 mg, 87% yield) was obtained as a colourless oil: [α]25D = −12.3 (c 0.70, CHCl3); 1H NMR (400 MHz, CDCl3) δ/ppm = 1.43 (s, 12H), 3.56 (dd, J = 5.2, 10.6 Hz, 1H), 3.63 (dd, J = 3.1, 10.6 Hz, 1H), 3.95 (ddd, J = 3.1, 5.2, 8.6 Hz, 1H), 4.22−4.30 (m, 4H), 4.36−4.40 (m, 1H), 4.57 (d, J = 12.0 Hz, 1H), 4.63 (d, J = 12.0 Hz, 1H), 5.61 (m, 1H), 7.28−7.37 (m, 5H); 13C NMR (100 MHz, CDCl3) δ/ppm = 23.8 (q), 26.9 (q), 60.0 (t), 60.8 (t), 69.4 (t), 73.5 (t), 78.4 (d), 80.1 (d), 102.1 (s), 109.2 (s), 127.6 (d), 127.7 (d), 128.3 (d), 128.5 (d), 137.3 (s), 137.9 (s); FT-IR (thin film) νmax (cm-1) 2987, 2933, 2862, 1373, 1218, 1088, 870, 738; MS (EI+) m/z (relative intensity %) 348 (M+, 1.3), 333 ([M–CH3]+, 1.2), 290 (4.7), 2.75 (2.4), 260 (4.2), 91 (100); HRMS (EI+) exact mass calculated for C20H28O5 (M+) m/z 348.1931, found m/z 348.1937. Elemental analysis calculated for C20H28O5: C, 68.94; H, 8.10; found: C, 68.74; H, 7.68.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3Supplementary File 4

Acknowledgments

This research was supported by the Spanish MICINN co-financed by the European Regional Development Fund (CTQ2008-06806-C02-01/BQU) and the Canary Islands Government, and projects PROIPRO 2/0006 and 7301 of San Luis University (UNSL), PIP 628 CONICET, and PIT 352-ANPCyT. D.D.D. is an Experienced Research Fellow of the Alexander von Humboldt Foundation. C.G. thanks the Spanish MICINN-FSE for a Ramón y Cajal contract.

References and Notes

  1. Philip, J.; Kocienski, P.J. Protective Groups, 3rd ed.; Georg Thieme Verlag: Stuttgart, Germany, 2005. [Google Scholar]
  2. Maarse, H. Volatile Compounds in Foods and Beverages; Marcel Dekker: New York, NY, USA, 1991; p. 554. [Google Scholar]
  3. Stuart, A.; Garrie, S.A.; Wolf-Jürgensen, P. Effects of fluocinolone acetonide cream on the skin window record of inflammatory exudates. J. Invest. Dermatol. 1971, 57, 343–346. [Google Scholar]
  4. Carreras, C.R.; García, C.E.; Martín, V.S.; Tonn, C.E.; Díaz, D.D.; Ceñal, J.P. (E)-2-((4R,5R)-5-((Benzyloxy)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-ene-1,4-diol. Molbank 2010, 2010, M676. [Google Scholar] [CrossRef]
  5. Armarego, W.L.F.; Perrin, D.D. Purification of Laboratory Chemicals, 4th ed.; Butterworth-Heinemann: Oxford, UK, 1996. [Google Scholar]
Scheme 1.
Scheme 1.
Molbank 2010 m680 sch001

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MDPI and ACS Style

Carreras, C.R.; García, C.E.; Martín, V.S.; Tonn, C.E.; Díaz, D.D.; Ceñal, J.P. (–)-5-[(4R,5R)-5-(Benzyloxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-4,7-dihydro-1,3-dioxepine. Molbank 2010, 2010, M680. https://doi.org/10.3390/M680

AMA Style

Carreras CR, García CE, Martín VS, Tonn CE, Díaz DD, Ceñal JP. (–)-5-[(4R,5R)-5-(Benzyloxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-4,7-dihydro-1,3-dioxepine. Molbank. 2010; 2010(2):M680. https://doi.org/10.3390/M680

Chicago/Turabian Style

Carreras, Carlos R., Celina E. García, Víctor S. Martín, Carlos E. Tonn, David Díaz Díaz, and Juan Pedro Ceñal. 2010. "(–)-5-[(4R,5R)-5-(Benzyloxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-4,7-dihydro-1,3-dioxepine" Molbank 2010, no. 2: M680. https://doi.org/10.3390/M680

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