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Volumn 128, Issue 16, 2006, Pages 5391-5403

Synthesis of a 10,000-membered library of molecules resembling carpanone and discovery of vesicular traffic inhibitors

Author keywords

[No Author keywords available]

Indexed keywords

FLUORESCENCE; NITROGEN; POLYSTYRENES; SUBSTITUTION REACTIONS; SYNTHESIS (CHEMICAL);

EID: 33646456511     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja056338g     Document Type: Article
Times cited : (73)

References (63)
  • 8
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    • (c) Schreiber, S. L. Science 2000, 287, 1964-1969.
    • (2000) Science , vol.287 , pp. 1964-1969
    • Schreiber, S.L.1
  • 10
    • 0042975166 scopus 로고    scopus 로고
    • (b) For an alternative theory on why nature produces diverse natural products, see: Firn, R. D.; Jones, C. G. Nat. Prod. Rep. 2003, 20, 382-391.
    • (2003) Nat. Prod. Rep. , vol.20 , pp. 382-391
    • Firn, R.D.1    Jones, C.G.2
  • 11
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    • and references therein
    • For a review on the integration of natural products in library synthesis, see: Paululat, T.; Tang, Y.-Q.; Grabley, S.; Thiericke, R. Chim. Oggi 1999, 17, 52-56 and references therein.
    • (1999) Chim. Oggi , vol.17 , pp. 52-56
    • Paululat, T.1    Tang, Y.-Q.2    Grabley, S.3    Thiericke, R.4
  • 16
    • 33646438242 scopus 로고    scopus 로고
    • note
    • Though technically a dienone, one of the dienone olefins in the scaffold is not in conjugation with the carbonyl, rendering it unreactive as a conjugate acceptor (vide infra),
  • 17
    • 33646437928 scopus 로고    scopus 로고
    • note
    • 15 confirmed that conjugate addition occurs diastereoselectively from the convex face of the enone.
  • 19
    • 33646463606 scopus 로고    scopus 로고
    • Institute for Chemistry and Cell Biology, Harvard University, Cambridge. MA
    • Institute for Chemistry and Cell Biology, Harvard University, Cambridge. MA.
  • 20
    • 0035961490 scopus 로고    scopus 로고
    • The standard resin used by the ICCB is a derivative of 500 μm polystyrene resin with a diisopropyl-p-methoxyphenylsilyl terminus. See: (a) Sternson, S. M.; Louca, J. B.; Wong, J. C.; Schreiber, S. L. J. Am. Chem. Soc. 2001, 123, 1740-1747.
    • (2001) J. Am. Chem. Soc. , vol.123 , pp. 1740-1747
    • Sternson, S.M.1    Louca, J.B.2    Wong, J.C.3    Schreiber, S.L.4
  • 23
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    • See ref 19
    • See ref 19.
  • 24
    • 0031317101 scopus 로고    scopus 로고
    • For an analysis of site-site interactions, see: Hodge, P. Chem. Soc. Rev. 1997, 26, 417-424.
    • (1997) Chem. Soc. Rev. , vol.26 , pp. 417-424
    • Hodge, P.1
  • 31
    • 33646463165 scopus 로고    scopus 로고
    • note
    • 1H NMR of product 16, which was cleaved from the resin with HF·pyridine.
  • 32
    • 33646458846 scopus 로고    scopus 로고
    • note
    • 1H NMR and mass recovery of 16, obtained by HF-pyridine-mediated cleavage of 18a and 18b from the resin. All subsequent studies showed that the mixture of 18a and 18b behaved as if it were one isomer. Furthermore, the distinction between 18a and 18b is transient. Following cleavage from the resin, both 18a and 18b yield the same product (16).
  • 34
    • 33646442345 scopus 로고    scopus 로고
    • See ref 24
    • (b) See ref 24.
  • 39
    • 33646451347 scopus 로고    scopus 로고
    • note
    • L-selectride, K-selectride. LAH, DIBAL-H, 9-BBN, and BH, each led to a complex mixture of products including products of over-reduction and allyl group cleavage.
  • 40
    • 33646438695 scopus 로고    scopus 로고
    • note
    • A mixture of oxime geometrical isomers was generally observed, in most cases with a ratio >4:1, presumably in favor of the E isomer where the oxime substituent is oriented away from the carpanone core.
  • 41
    • 33646462314 scopus 로고    scopus 로고
    • note
    • 1H NMR spectra for all numbered compounds produced in the solid phase are included in the Supporting Information.
  • 43
    • 33646458696 scopus 로고    scopus 로고
    • note
    • Depending on the thiol, the outcomes included no reaction, 1,4-thiol incorporation only, oxime formation only, and the desired MCR. The results could not be correlated with the structure of the thiol.
  • 48
    • 33646456485 scopus 로고    scopus 로고
    • note
    • We speculate that the increased coordinating capability of highly nitrogenated triazoles and ureas might deliver palladium to the allyl group nearest these functional groups, thus promoting undesired cleavage of the ketal allyl group.
  • 49
    • 0000456170 scopus 로고
    • Oxidative coupling of phenols and phenol ethers
    • Trost, B. M., Fleming, I., Pattenden, G., Eds.; Pergamon: Oxford
    • For general reviews, see: (a) Whiting, D. A. Oxidative Coupling of Phenols and Phenol Ethers. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Pattenden, G., Eds.; Pergamon: Oxford, 1991: Vol. 3, pp 659-703.
    • (1991) Comprehensive Organic Synthesis , vol.3 , pp. 659-703
    • Whiting, D.A.1
  • 52
    • 33646453784 scopus 로고    scopus 로고
    • note
    • Due to the statistical improbability ot splitting any mixture of solid-phase resin beads into identical heterogeneous batches, a certain percentage of the theoretical number of compounds in any split-and-pool library will not be made. This percentage is minimised when multiple copies of the library are prepared. Three copies of the carpanone library were prepared.
  • 54
    • 33646460766 scopus 로고    scopus 로고
    • See ref 17c
    • (b) See ref 17c.
  • 55
    • 33646465294 scopus 로고    scopus 로고
    • note
    • This process is known as position encoding.
  • 57
    • 33646464842 scopus 로고    scopus 로고
    • See ref 2
    • (b) See ref 2.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.