Solid-phase synthesis of small molecule libraries using double combinatorial chemistry

Tetrahedron Letters

Volumn 38, Issue 11, 1997, Pages 2011-2014

  Nielsen, John ^a   Jensen, Flemming R ^a  

^a TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CARBROMAL;

ALKYLATION; ARTICLE; CHEMICAL REACTION; DRUG SYNTHESIS; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; SOLID;

EID: 0031575797     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)00219-0     Document Type: Article

References (14)

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2. (b) Petsko, G. A. Nature 1996, 384, 1 (supplement to issue 6604).
3. 2. Tong, G; Nielsen, J. Bioorg. Med. Chem. 1996, 4(5), 693-698.
4. 3. Pavia, M. R.; Cohen, M. P.; Dilley, G. J.; Dubuc, G. R.; Durgin, T. L.; Forman, F. W.; Hediger, M. E.; Milot, G.; Powers, T. S.; Sucholeiki, I.; Zhou, S.; Hangauer, D. G. Bioorg. Med. Chem. 1996, 4, 659-666.
5. 4. Acylation of the tyrosine hydroxyl can be a severe side reaction. However, careful control of reaction conditions lead to only minimum amount of O-acylated product (approximately 2-3%, by HPLC-analysis). The applied condition were FmocTyr-OH/DIPEA/HBTU (eq. amounts, approximately 1.1 eq. to resin) in DMF, double coupling (30 minutes + 25 minutes), room temperature.
6. 5. a) Mitsunobu, O.; Yamada, M. Bull. Chem. Soc. Japan 1967, 40, 2380-2382;
7. b) Mitsunobu, O.; Yamada, M.; Mukaiyama, T. Bull. Chem. Soc. Japan 1967, 40, 935-939;
8. c) Mitsunobu, O. Synthesis 1981, 1-28.
9. 6. Rano, T. A.; Chapman, K. T. Tetrahedron Lett. 1995, 36, 3789-3792.
10. 7. Kates, S.A.; Daniels, S.B.; Albericio, F. Anal. Biochem., 1993, 212, 303-310
11. 8. See. e.g. a) Carpino, L.A. J. Am. Chem. Soc. 1993, 115, 4397-4398;
12. b) Carpino, L. A.; El-Feham, A.; Albericio, F. Tetrahedron Lett. 1994, 35, 2279-2282.
13. 2 = H) originating from the statistically most unlikely recombination of the two unalkylated species 1 with 5 should be present in approximately 1% but was not detected.
14. 10. A double combinatorial library obtained by combining two libraries of respectively n and m members yields a third library of n × m members. When two identical libraries of n members are combined, the number of members in the combined library will be 1/2 × n × (n+1).