Enantiospecific synthesis and cytotoxicity of 7-(4-methoxyphenyl)-6-phenyl-2,3,8,8a-tetrahydroindolizin-5(1H)-one enantiomers

Bioorganic and Medicinal Chemistry

Volumn 16, Issue 8, 2008, Pages 4367-4377

  Kimball, F Scott ^a   Turunen, Brandon J ^a   Ellis, Keith C ^a   Himes, Richard H ^a   Georg, Gunda I ^a  

^a UNIVERSITY OF KANSAS   (United States)

Author keywords

Colon cancer; Enantiospecific synthesis; HCT 116; Tetrahydroindolizinones

Indexed keywords

7 (4 METHOXYPHENYL) 6 PHENYL 2,3,8,8A TETRAHYDROINDOLIZIN 5 (1H)ONE; ANTINEOPLASTIC AGENT; TYLOPHORINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BIOASSAY; CONTROLLED STUDY; CYTOTOXICITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; ENANTIOSELECTIVITY; HUMAN; HUMAN CELL;

CELL SURVIVAL; HCT116 CELLS; HUMANS; INDOLIZINES; MOLECULAR STRUCTURE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 42149167560     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2008.02.073     Document Type: Article

References (10)

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4. For related investigations of the tetrahydroindolizin-5(1H)-one core see. Sharma V.M., Adi Seshu K.V., Vamsee Krishna C., Prasanna P., Chandra Sekhar V., Venkateswarlu A., Rajagopal S., Ajaykumar R., Deevi D.S., Rao Mamidi N.V.S., and Rajagopalan R. Bioorg. Med. Chem. Lett. 13 (2003) 1679
5. Chiralcel OJ, elution with 20-50% isopropanol in hexanes, flow rate 5 mL/min. Retention time for (+)-2 of 15 min. Retention time of 20.8 min for (-)-2.
6. 3), mp 199.5-201.4 °C (acetone); (±)-2: colorless crystals, mp 184.8-186.4 °C (acetone).
7. The enantiomeric ratio varied between experiments from 50:50 (racemic) to 60:40 (+)-(S)-2:(-)-(R)-2.
8. Some degree of racemization was noticed in step e, with the isolation of 5% yield of the O-benzyl, N-benzyl side-product. This product was isolated in a 60:40 dr suggesting that perhaps the racemization does not require strong acid to occur. Furthermore, this side-product also indicated, that either the BOC-protected amine or the free amine, rather than the amine salt, are prone to racemization.
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