Synthesis of second-generation Sansalvamide A derivatives: Novel templates as potential antitumor agents

Journal of Organic Chemistry

Volumn 72, Issue 6, 2007, Pages 1980-2002

  Rodriguez, Rodrigo A ^a   Pan, Po Shen ^a   Pan, Chung Mao ^a   Ravula, Suchitra ^a   Lapera, Stephanie ^a   Singh, Erinprit K ^a   Styers, Thomas J ^a   Brown, Joseph D ^a   Cajica, Julia ^a   Parry, Emily ^a   Otrubova, Katerina ^a   McAlpine, Shelli R ^a  

^a SAN DIEGO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTITUMOR POTENCY; CANCER CELLS; CONFORMATIONAL SPACE; SANSALVAMIDE A DERIVATIVES;

CONFORMATIONS; DERIVATIVES; HYDROGEN BONDS; STEREOCHEMISTRY; SYNTHESIS (CHEMICAL); TUMORS;

AMIDES;

ALKYL GROUP; AMIDE; AMINO ACID; ANTINEOPLASTIC AGENT; AROMATIC AMINO ACID; DEPSIPEPTIDE; MACROCYCLIC COMPOUND; METHYL GROUP; SANSALVAMIDE A DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER CELL; CANCER CELL CULTURE; COLON CANCER; CONTROLLED STUDY; CYTOTOXICITY; DRUG CONFORMATION; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HYDROGEN BOND; HYDROPHOBICITY; MELANOMA; PANCREAS CANCER; PROSTATE CANCER; STEREOCHEMISTRY;

AMINO ACIDS; ANTINEOPLASTIC AGENTS; DEPSIPEPTIDES; HYDROGEN BONDING; MOLECULAR CONFORMATION; STEREOISOMERISM;

EID: 33947246678     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo061830j     Document Type: Article

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15. water), is a well established measure of the compound's hydrophilicity. Low hydrophilicities and therefore high log P values cause poor absorption or permeation. It has been shown for compounds to have a reasonable probability of being well absorb their log P value must not be greater than 5.0. The distribution of calculated log P values of more than 3000 drugs on the market underlines this fact.
16. 1H NMR were taken for cyclized peptides, but due to their complexity, they were not seen as the primary confirmation for cyclized compounds.) See Supporting Information for spectra.
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21. For details on the reaction conditions see Supporting Information.
22. The dodecapeptide tends to form at cyclization concentrations greater than 0.005 M. We found that cyclizing the linear pentapeptide at 0.004 M led to almost exclusively the pentapeptide macrocycle as the product.
23. It was straightforward to follow the reactions via LCMS as the starting material double deprotected linear precursor would appear at 5.0-5.5 min and the cyclized product would appear between 6.1-7.0 min. (24) The 34 macrocyclic peptides have LCMS spectra given in the Supporting Information. In addition, 29 compounds out of 34 in the library have each intermediate characterized via NMR and/or LCMS.
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26. See Supporting Information for all compound structures shown in the cytotoxicity assays.