Solid-phase synthesis of a type II′ β-turn peptido-mimetic library

Tetrahedron Letters

Volumn 44, Issue 19, 2003, Pages 3835-3838

  Grimes Jr , John H ^a   Angell, Yvonne M ^b   Kohn, Wayne D ^a  

^a ELI LILLY AND COMPANY   (United States)

^b AFFYMAX RESEARCH INSTITUTE   (United States)

Author keywords

IBTM; Pictet Spengler reaction; Solid phase synthesis; turn mimetics

Indexed keywords

2 AMINO 3 OXOHEXAHYDROINDOLIZINO[8,7 B]INDOLE 5 CARBOXYLATE; 4 [N [1 (4,4 DIMETHYL 2,6 DIOXOCYCLOHEXYLIDENE) 3 METHYLBUTYL]AMINO]BENZYL ESTER; ALDEHYDE; ASPARTIC ACID; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; CARBOXYLIC ACID DERIVATIVE; DIPEPTIDE; ESTER DERIVATIVE; TRYPTOPHAN; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; CHEMICAL REACTION; COMBINATORIAL CHEMISTRY; DRUG SYNTHESIS; LACTAMIZATION; LIBRARY; PICTET SPENGLER REACTION; SOLID; STEREOCHEMISTRY;

EID: 0037420751     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)00701-9     Document Type: Article

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13. The color of the reaction mixture was always yellowish. When a Kaiser test no longer showed blue, the resin would be removed, washed, and a small amount would be cleaved to check the molecular weight of the intermediate Pictet-Spengler product. Sometimes this would show that the γ-lactamization had not reached completion. If the resin was then resubjected to the Pictet-Spengler conditions, the reaction mixture would turn to a red color, and LC/MS would show decomposition.
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15. 3 OH:anisole:triisopropylsilane for 2 h. The resin was then filtered off and the TFA solution concentrated to <200 μL on a rotory evaporator. The peptides were precipitated with 15 ml diethyl ether to obtain the final crude compounds.
16. Library synthesis was carried out in a 96 well 'plate' format using the same synthesis procedure as that used for 8 and 9 . Cleavage was carried out as above, except that the TFA solution was concentrated to <200 μL using a Genevac HT-4 evaporator. All products were characterized by analytical HPLC and found to have the correct molecular weight by MALDI-TOF MS within ±1 a.m.u.
17. 2), 50.7 (CH), 51.2 (CH), 51.5 (CH), 51.6 (CH), 56.5 (CH), 57.3 (CH), 58.6 (CH), 111.8 (CH), 118.6 (CH), 119.3 (CH), 121.8 (CH), 127.4 (CH), 127.6 (CH), 128.4 (CH).