메뉴 건너뛰기




Volumn 121, Issue 39, 1999, Pages 9073-9087

Synthesis and preliminary evaluation of a library of polycyclic small molecules for use in chemical genetic assays

Author keywords

[No Author keywords available]

Indexed keywords

CARBOXYLIC ACID; DISCODERMOLIDE; NATURAL PRODUCT; PACLITAXEL; RAPAMYCIN; SHIKIMIC ACID; TRAPOXIN; UNCLASSIFIED DRUG;

EID: 0032879750     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja992144n     Document Type: Article
Times cited : (163)

References (107)
  • 2
    • 0344817409 scopus 로고    scopus 로고
    • accessed Jun
    • Schreiber Group Website. http://www-schreiber.chem.harvard.edu (accessed Jun 1999).
    • (1999)
  • 22
    • 0344385650 scopus 로고    scopus 로고
    • accessed Jun
    • Rapp Polymere Home Page. http://www.rapp-polymere.com (accessed Jun 1999).
    • (1999)
  • 29
    • 0345248492 scopus 로고    scopus 로고
    • note
    • Tamura et al. propose reaction of the Z-nitrone via an exo transition state. However, orbital overlap appears to be more favorable in the reaction of the E-nitrone via an endo transition state as indicated in Scheme 1.
  • 33
    • 0345248490 scopus 로고    scopus 로고
    • note
    • All resin-bound products were photocleaved and analyzed by standard techniques (TLC, HPLC, NMR, MS).
  • 36
    • 0345248489 scopus 로고    scopus 로고
    • note
    • Abbreviations not cited in text: DMF = N,N-dimethylformamide, DMA = N,N-dimethylacetamide, NMP = N-methylpyrrolidinone, PyBroP = bromotripyrrolidinophosphonium hexafluorophosphate, HATU = N-[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridin-1-ylmethylene]-N- methylmethan-aminium hexafluorophosphate, PyBOP = benzotriazol-1-yloxytripyrroli-dinophosphonium hexafluorophosphate, TFFH = N,N,N′,N′-tetramethylfluoroformamidinium hexafluorophosphate, DIPC = 1,3-diisopropylcarbodiimide, CDI = 1,1′-carbonyldiimidazole, DIPEA = N,N-diisopropylethylamine, DMAP = 4-(dimethylamino)pyridine, cod = 1,5-cyclooctadiene, DPPF = 1,1′-bis(diphenylphosphino)ferrocene, DBN = 1,5-diazabicyclo[4.3.0]non-5-ene, LC-MS = tandem high-pressure liquid chromatography-mass spectrometry, HR-FAB-MS = high-resolution fast atom bombardment mass spectrometry, HR-TOF-ESI-MS = high-resolution time-of-flight electrospray induction mass spectrometry, EC-GC = electron capture detection gas chromatography.
  • 37
    • 0345680152 scopus 로고    scopus 로고
    • note
    • The term "building block" is preferred over the commonly used term "monomer" since the products are non-oligomeric.
  • 55
    • 0000633011 scopus 로고
    • Trost, B. M., Fleming, I., Eds.; Permangon Press: Oxford
    • Heck, R. F. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Permangon Press: Oxford, 1991; Vol. 4, pp 833-863.
    • (1991) Comprehensive Organic Synthesis , vol.4 , pp. 833-863
    • Heck, R.F.1
  • 60
    • 0344385618 scopus 로고    scopus 로고
    • note
    • 3-Bn, 69% side reaction; R = 4-I-Bn, 59%; R = 4-Cl-Bn, 32%; R = Bn, 24%; R = 4-tBu-Bn, 13%; R = 3-I-Bn, 46%; R = 2-I-Bn, 31%.) Replacement of the ω-aminocaproic acid spacer with glycine or removal of the spacer altogether actually decreases the amount of 10 formed. (For 12, R = 4-I-Bn: Aca spacer, 59% side reaction; Gly spacer, 36%; no spacer 29%.) Interestingly, substitution at the benzylic carbon eliminates the side reaction altogether (for 12, R = 4-I-α-Me-Bn, 0% side reaction). Moreover, solution-phase aminolysis of the tetracycle below results in no side reaction. Control experiments verified that the side reaction is not caused by photocleavage. (illustration presented)
  • 61
    • 0345680137 scopus 로고    scopus 로고
    • note
    • Aminolysis in the presence of sodium cyanide in MeOH, sodium hydride in DMA, sodium methoxide in benzene, ferric chloride in MeOH, lithium chloride in MeOH, and lithium hydroxide in MeOH all appeared to result in degradation of the linker. Aminolysis in the presence of the Otera organotin catalyst in toluene did not reduce the amount of epoxycyclohexenol recovered.
  • 70
    • 0001391308 scopus 로고
    • Wiley & Sons: New York, Collect.
    • Kamm, O. Organic Syntheses; Wiley & Sons: New York, 1941; Collect. Vol. I, pp 445-447.
    • (1941) Organic Syntheses , vol.1 , pp. 445-447
    • Kamm, O.1
  • 71
    • 0344817352 scopus 로고    scopus 로고
    • note
    • 2; and (7) esterification with the Otera organotin catalyst.
  • 72
    • 0345680135 scopus 로고    scopus 로고
    • note
    • Despite considerable efforts to understand this vexing side reaction, both its exact mechanism and a rationalization of the ameliorating effects of alkynylbenzyl substituents remain mysterious to us.
  • 82
    • 0345248472 scopus 로고    scopus 로고
    • The 1996-1997 Aldrich Structure Index lists 24 applicable salicyl aldehydes
    • The 1996-1997 Aldrich Structure Index lists 24 applicable salicyl aldehydes.
  • 83
    • 0345248471 scopus 로고    scopus 로고
    • note
    • The 1996-1997 Aldrich Structure Index lists 54 applicable symmetrical anhydrides compared to over 1000 carboxylic acids.
  • 86
    • 0344817348 scopus 로고    scopus 로고
    • Certain acid-sensitive products were also analyzed by TLC and FABMS
    • Certain acid-sensitive products were also analyzed by TLC and FABMS.
  • 88
    • 0345248470 scopus 로고    scopus 로고
    • note
    • n = X, where X represents all eight building blocks at a given position.
  • 100
    • 0344817315 scopus 로고    scopus 로고
    • FACS Screening Web Page, accessed Jun
    • Nolan, G. P., FACS Screening Web Page, http://www.stanford.edu/ group/nolan/FACSscrn.html (accessed Jun 1999).
    • (1999)
    • Nolan, G.P.1
  • 101
    • 0345248427 scopus 로고    scopus 로고
    • Based upon previous results, a 50% yield was assumed
    • Based upon previous results, a 50% yield was assumed.
  • 102
    • 0344385577 scopus 로고    scopus 로고
    • The rapamycin concentration was 100 nM. J. Huang and S. L. S., unpublished results
    • The rapamycin concentration was 100 nM. J. Huang and S. L. S., unpublished results.
  • 103
    • 0345248426 scopus 로고    scopus 로고
    • unpublished results
    • R. W. King, unpublished results.
    • King, R.W.1


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.