First total synthesis of N-4909 and its diastereomer; a stimulant of apolipoprotein E secretion in human hepatoma Hep G2 cells.

Abstract

Both (R)- and (S)-3-hydroxy-13-methyltetradecanoic acids were prepared via a lipase-catalyzed enantioselective acylation. The total synthesis of N-4909 and its diastereomer were achieved by a coupling of either (R)- or (S)-3-hydroxy-13-methyltetradecanoic acid moiety with a hexapeptide moiety and by a cyclization with HATU (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) and HOAt (1-hydroxy-7-azabenzotriazole) in a high dilution condition. The R configuration of 3-hydroxy-13-methyltetradecanoic acid was found to be important for stimulating the activity of apolipoprotein E secretion in human hepatoma Hep G2 cells.

• Authors: M Yanai, S Hiramoto
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 52 Issue 2 Pg. 150-9 (Feb 1999) ISSN: 0021-8820 [Print] England
• PMID: 10344569 (Publication Type: Journal Article)

Chemical References

• 3-hydroxy-13-methyltetradecanoic acid
• Apolipoproteins E
• Hypolipidemic Agents
• Peptides, Cyclic

Topics

• Animals
• Apolipoproteins E (metabolism)
• Humans
• Hypolipidemic Agents (chemical synthesis, chemistry, pharmacology)
• Liver Neoplasms, Experimental (metabolism, pathology)
• Peptides, Cyclic (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism
• Tumor Cells, Cultured