First total synthesis of N-4909 and its diastereomer; a stimulant of apolipoprotein E secretion in human hepatoma Hep G2 cells.
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.
Yanai
M
M
1st Pharmaceutical Laboratory, Pharmaceutical Research Laboratories, Nisshin Flour Milling Co., Ltd., Saitama, Japan.
Hiramoto
S
S
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
C102440:3-hydroxy-13-methyltetradecanoic acid; D001057:Apolipoproteins E; D000960:Hypolipidemic Agents; D010456:Peptides, Cyclic