ChemInform Abstract: STEREOSPECIFIC SYNTHESIS OF TRANS‐1,3‐DISUBSTITUTED‐1,2,3,4‐TETRAHYDRO β‐CARBOLINES

Ungemach, Frank S.; DIPIERRO, M.; Weber, Robert; Cook, James

doi:10.1002/chin.197949231

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“…The trans-isomer was determined to be the major product based upon calculations of the products of the subsequent allenic cycloisomerization reaction (see Supporting Information). 24,25 Allene-containing tetrahydro-β-carbolines 20a-b were next subjected to a Ag(I)-catalyzed cycloisomerization reaction (Scheme 3). 22 Reaction of tetrahydro-β-carboline derivative 20a{1,2,0} with 20 mol % silver nitrate in acetone in a vial wrapped in aluminum foil for 18 h afforded 21a{1,2,0} in 56% yield.…”

Section: ' Results and Discussionmentioning

confidence: 99%

Diverging DOS Strategy Using an Allene-Containing Tryptophan Scaffold and a Library Design that Maximizes Biologically Relevant Chemical Space While Minimizing the Number of Compounds

et al. 2011

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A diverging diversity-oriented synthesis (DOS) strategy using an allene-containing tryptophan as a key starting material was investigated. An allene-yne substituted derivative of tryptophan 12 gave indolylmethylazabicyclooctadiene 17 when subjected to a microwave-assisted allenic [2 + 2] cycloaddition reaction. This same tryptophan-derived precursor afforded an indolylmethyldihydrocyclopentapyridinone 14 when subjected to a rhodium(I)-catalyzed cyclocarbonylation reaction and an indolylmethylpyrrolidinocyclopentenones 16 when reacted with molybdenum hexacarbonyl. Construction of allenic tetrahydro-β-carboline scaffolds via a Pictet-Spengler reaction and subsequent silver(I)-catalyzed cycloisomerization afforded tetrahydroindolizinoindoles (21). Attachment of allene and alkyne groups to the tetrahydro-β-carboline followed by a microwave-assisted allenic [2 + 2] cycloaddition reaction provided tetrahydrocyclobutaindoloquinolizinones 24 and the tetrahydrocyclopentenone indolizinoindolone 26 when reacted with molybdenum hexacarbonyl. These six scaffolds were used as a template for the construction of a virtual library of 11,748 compounds employing 44 indoles, 12 aldehydes, and 51 alkynes. Diversity analyses using a combination of cell-based chemistry space computations using BCUT (Burden (B) CAS (C) Pearlman at the University of Texas (UT)) metrics and Tanimoto coefficient (Tc) similarity calculations using two-dimensional (2D) fingerprints showed that the compounds in the virtual library occupied new chemical space when compared to the 327,000 compounds in the molecular libraries small molecule repository (MLSMR). A subset of fifty-three compounds was identified from the virtual library using the DVS package of Sybyl 8.0; this subset represents the most diverse compounds within the chemical space defined by these compounds and will be synthesized and screened for biological activity.

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Section: ' Results and Discussionmentioning

confidence: 99%