Efficient total synthesis of 12-oxo-PDA and OPC-8:0.
Although the supply of 12-oxo-PDA (1) and OPC-8:0 (2), the metabolites in the linolenic acid cascade leading to epi-jasmonic acid, is in demand for biological investigations, the previous syntheses of these metabolites suffer from low efficiency. Recently, we established a reaction to install an alkyl group onto the ring of cyclopentene monoacetate 4 by using a reagent system consisting of RMgCl (3 equiv) and CuCN (cat). The reaction was applied to ClMg(CH2)8OTBDPS (11) with modification by which the quantity of 11 could be reduced to 2 equiv without decreasing efficiency. The product 12 obtained in 88% yield with 92% regioselectivity was successfully transformed into the key iodo-lactone 17 in good yield, from which 12-oxo-PDA (1) and OPC-8:0 (2) were synthesized as described in Schemes 3 and 5 through construction of the cis side chain by Wittig reaction. Note that the Wittig reaction proceeded with high cis selectivity of >95%, which is higher than in similar cases reported previously. Synthesis of the 13-isomers of 1 and 2 was also accomplished. With these compounds in hand, the epimerization speed of 1 and 2 was investigated to rule out overestimation of the finding in the literature that 1 and 2 change to the 13-epimers easily. Instead, we observed that the compounds are quite stable at room temperature for an extended period of days under slightly acidic and neutral conditions.
D000478:Alkylation; D002210:Caprylates / Q000138:chemical synthesis* / Q000737:chemistry; D003517:Cyclopentanes / Q000737:chemistry / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis*; D054883:Oxylipins; D013237:Stereoisomerism; D017962:alpha-Linolenic Acid / Q000378:metabolism
C483358:8-(3-oxo-2-cis-((Z)-2-pentenyl)cyclopentyl)octanoic acid; D002210:Caprylates; D003517:Cyclopentanes; D005231:Fatty Acids, Unsaturated; D054883:Oxylipins; D017962:alpha-Linolenic Acid; C025999:12-oxophytodienoic acid; C011006:jasmonic acid