메뉴 건너뛰기
Angewandte Chemie - International Edition
Volumn 49, Issue 11, 2010, Pages 2045-2049
Total synthesis of myrtucommulone A
Author keywords

Alkylation; Apoptosis; Michael addition; Natural products; Total synthesis
Indexed keywords

ANTI-INFLAMMATORIES; APOPTOSIS; CHEMICAL EQUATIONS; MICHAEL ADDITIONS; MYRTUS COMMUNIS; NATURAL PRODUCTS; TOTAL SYNTHESIS;
EID: 77949341640     PISSN: 14337851     EISSN: 15213773     Source Type: Journal    
DOI: 10.1002/anie.200903906     Document Type: Article
Times cited : (62)
References (51)
  • 7
    • 50149106958 scopus 로고    scopus 로고
    • vgl. auch A. Rosa, M. P. Melis, M. Deiana, A. Atteri, G. Appendino, G. Corona, A. Inacani, D. Loru, M. A. Dessi, Chem. Phys. Lipids 2008, 155, 16-22.
    • b) vgl. auch A. Rosa, M. P. Melis, M. Deiana, A. Atteri, G. Appendino, G. Corona, A. Inacani, D. Loru, M. A. Dessi, Chem. Phys. Lipids 2008, 155, 16-22.
  • 14
    • 77949408422 scopus 로고    scopus 로고
    • International Patent PCT/EP 2009/006226
    • J. Jauch, International Patent PCT/EP 2009/006226, 2009.
    • (2009)
    • Jauch, J.1
  • 15
    • 37049153835 scopus 로고    scopus 로고
    • In a comparable reaction McGookin et al. synthesized flavaspidic acid (19% yield) from 3-methylbutyryl phloroglucinol, butyrylfilixic acid, and paraformaldehyd. See A. McGookin, A. Robertson, T. H. Simpson, J. Chem. Soc. 1953, 1828-1829
    • In a comparable reaction McGookin et al. synthesized flavaspidic acid (19% yield) from 3-methylbutyryl phloroglucinol, butyrylfilixic acid, and paraformaldehyd. See A. McGookin, A. Robertson, T. H. Simpson, J. Chem. Soc. 1953, 1828-1829.
  • 36
    • 77949412478 scopus 로고    scopus 로고
    • Myrtucommulone A (1) is a complex mixture of different rotamers, which are stabilized by intramolecular hydrogen bonds. Additionally, there are probably numerous keto-enol equilibria, which lead to more complex 1H and 13C NMRspectra. Appendino et al.[3a] silylated myrtucommulon A in 23% yield. The silylated derivative could be characterized by NMR spectroscopy. According to these authors, methylation and other derivatization methods led to complete decomposition. Quinn et al.[6] reported recently on detailed 2D NMR studies of 1 and the myrtucommulones F-I. These authors conclude that the relative configuration in 1 for both asymmetric centers is R*. This is consistent with the formula shown in Ref, 6, However, later in their publication, these authors state that 1 occurs in the meso form and that optical activity is due to atropisomers, which are stabilized by hydrogen bonding. The method for
    • [6] reported recently on detailed 2D NMR studies of 1 and the myrtucommulones F-I. These authors conclude that the relative configuration in 1 for both asymmetric centers is R*. This is consistent with the formula shown in Ref. [6]. However, later in their publication, these authors state that 1 occurs in the meso form and that optical activity is due to atropisomers, which are stabilized by hydrogen bonding. The method for structure elucidation presented here (via 11a and 11b) is unambiguous; the derivatization is almost quantitative and thus superior to other methods.
  • 37
    • 77949379787 scopus 로고    scopus 로고
    • R( 11b)=12.58 min. (see the Supporting Information). Interestingly, only linear pentacyclic derivatives formed. Angular derivatives could not be detected.
    • R( 11b)=12.58 min. (see the Supporting Information). Interestingly, only linear pentacyclic derivatives formed. Angular derivatives could not be detected.
  • 38
    • 33746342493 scopus 로고    scopus 로고
    • The ratio between 11a and 11b is 54:46 (see the Supporting Information). The double Friedel-Crafts alkylation occurs with low-level simple diastereoselectivity in favor of the chiral myrtucommulone A. To our knowledge, this is the first example of a double intermolecular Friedel-Crafts alkylation, in which a benzylic stereogenic center influences the configuration of the newly formed stereogenic center in meta position (see also the Supporting Information and A. J. Lampkins, O. Abdul-Rahim, R. K. Castellano, J. Org. Chem. 2006, 71, 5815-5818);
    • The ratio between 11a and 11b is 54:46 (see the Supporting Information). The double Friedel-Crafts alkylation occurs with low-level simple diastereoselectivity in favor of the chiral myrtucommulone A. To our knowledge, this is the first example of a double intermolecular Friedel-Crafts alkylation, in which a benzylic stereogenic center influences the configuration of the newly formed stereogenic center in meta position (see also the Supporting Information and A. J. Lampkins, O. Abdul-Rahim, R. K. Castellano, J. Org. Chem. 2006, 71, 5815-5818);
  • 39
    • 64349087238 scopus 로고    scopus 로고
    • Diastereoselective Friedel-Crafts alkylations with chiral alkylating reagents have been studied. See for example: a A. C. Silvanus, S. J. Heffernan, D. J. Liptrot, G. Kociok-Köhn, B. I. Andrews, D. R. Carbery, Org. Lett. 2009, 11, 1175-1178;
    • Diastereoselective Friedel-Crafts alkylations with chiral alkylating reagents have been studied. See for example: a) A. C. Silvanus, S. J. Heffernan, D. J. Liptrot, G. Kociok-Köhn, B. I. Andrews, D. R. Carbery, Org. Lett. 2009, 11, 1175-1178;
  • 41
    • 77949395842 scopus 로고    scopus 로고
    • D. Stadler, T. Bach, Angew. Chem. 2008, 120, 7668-7670; Angew. Chem. Int. Ed. 2008, 47, 7557-7559;
    • c) D. Stadler, T. Bach, Angew. Chem. 2008, 120, 7668-7670; Angew. Chem. Int. Ed. 2008, 47, 7557-7559;
  • 47
  • 48
    • 77949342403 scopus 로고    scopus 로고
    • X-ray analysis of 1: C38H52O10, bright yellow crystals, Mr= 667.79 gmol-1; triclinic, space group P1̄: a=10.494(1, b= 12.436(1, c=14.305(2) Å, α=81.755(7, β=89.403(7, γ= 75.669(7)°, V=1789.5(4) Å3, Z=2, μ(Mo Kα)=1.239 mm-1, T= 120 K, F(000)=718. Data were collected on a Bruker-AXS X8Apex diffractometer. 47122 reflections up to 2θmax=60° were registered, of which 10236 independent reflections were used for all calculations. The structure was solved by direct methods and anisotropically refined with all non-hydrogen atoms.[22] The hydrogen atoms were treated as rigid groups with idealized geometry at their carbon atoms. The isopropyl groups C12 and C26 are disordered according to the potential isomers and were refined at split-atom positions. The refinement
    • [22] The hydrogen atoms were treated as rigid groups with idealized geometry at their carbon atoms. The isopropyl groups C12 and C26 are disordered according to the potential isomers and were refined at split-atom positions. The refinement with I>2σ(I) resulted in a final R1=0.058, wR2=0.15. CCDC 640674 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data-request/cif.
  • 49
    • 52649119793 scopus 로고    scopus 로고
    • 2 synthase 1 was analyzed in the microsomal preparation of interleukion-1β-stimulated A549 lung epithelial carcinoma cells. See: A. Koeberle, U. Siemoneit, U. Bühring, H. Northoff, S. Laufer, W. Albrecht, O. Werz, J. Pharmacol. Exp. Ther. 2008, 326, 975-982. The induction of apoptotic cell death of human promyelocytic leukemia cells (HL-60) was analyzed after 24 h incubation by MTT assay. See Ref. [7b].
    • 2 synthase 1 was analyzed in the microsomal preparation of interleukion-1β-stimulated A549 lung epithelial carcinoma cells. See: A. Koeberle, U. Siemoneit, U. Bühring, H. Northoff, S. Laufer, W. Albrecht, O. Werz, J. Pharmacol. Exp. Ther. 2008, 326, 975-982. The induction of apoptotic cell death of human promyelocytic leukemia cells (HL-60) was analyzed after 24 h incubation by MTT assay. See Ref. [7b].
  • 50
    • 77949364142 scopus 로고    scopus 로고
    • Recrystallization from methanol yields an amorphous powder with a melting point of 183-185°C; Ref. [1]: 185-186°C. Natural 1, which was not recrystallized from methanol, also showed a melting range from 150-180°C.
    • Recrystallization from methanol yields an amorphous powder with a melting point of 183-185°C; Ref. [1]: 185-186°C. Natural 1, which was not recrystallized from methanol, also showed a melting range from 150-180°C.

* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.