Baertschi S W, Ingram C D, Harris T M, Brash A R
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232.
Biochemistry. 1988 Jan 12;27(1):18-24. doi: 10.1021/bi00401a004.
cis-12-Oxophytodienoic acid (cis-12-oxo-PDA) is a C18 cyclopentenone formed from the 13-(S)-hydroperoxide of linolenic acid in flaxseed and other plant tissues. Although the structure of cis-12-oxo-PDA is well established, the absolute configuration of the side chains has not been determined. We have now measured this important parameter by two independent approaches. The CD spectrum of freshly prepared cis-12-oxo-PDA showed no deviations from base line--implying that the product is racemic. This conclusion was checked by a high-pressure liquid chromatography (HPLC) method capable of resolving the enantiomers; cis-12-oxo-PDA was reduced to two saturated hydroxy analogues which were each converted to (-)-menthoxycarbonyl diastereomers and analyzed by HPLC. Each epimer was resolved as two peaks of equal area, thus confirming that their cis-12-oxo-PDA parent is a racemic mixture, enantiomeric at the ring junctures. We propose that the biosynthesis of racemic cis-12-oxo-PDA proceeds by dehydration of the 13(S)-hydroperoxide to an allene oxide. A major fate of the allene oxide is hydrolysis to an alpha-ketol, which is always formed together with cis-12-oxo-PDA. The allene oxide also opens to a zwitterion, which undergoes charge delocalization to form a planar intermediate; this structure is the achiral precursor of the stable end product of pericyclic ring closure, viz., racemic cis-12-oxo-PDA.
顺式-12-氧代植物二烯酸（cis-12-oxo-PDA）是一种C18环戊烯酮，由亚麻籽和其他植物组织中亚麻酸的13-(S)-氢过氧化物形成。尽管顺式-12-氧代-PDA的结构已明确，但侧链的绝对构型尚未确定。我们现在通过两种独立的方法测量了这一重要参数。新制备的顺式-12-氧代-PDA的圆二色光谱（CD）未显示基线偏差，这意味着该产物是外消旋的。这一结论通过一种能够拆分对映体的高压液相色谱（HPLC）方法进行了验证；顺式-12-氧代-PDA被还原为两种饱和羟基类似物，每种类似物都转化为(-)-薄荷氧基羰基非对映异构体并通过HPLC进行分析。每个差向异构体都被拆分为两个面积相等的峰，从而证实其顺式-12-氧代-PDA母体是一种外消旋混合物，在环连接处呈对映体。我们认为外消旋顺式-12-氧代-PDA的生物合成是通过13(S)-氢过氧化物脱水生成丙二烯氧化物进行的。丙二烯氧化物的一个主要归宿是水解为α-酮醇，它总是与顺式-12-氧代-PDA一起形成。丙二烯氧化物也会开环形成两性离子，该两性离子会发生电荷离域形成平面中间体；这种结构是周环闭环稳定终产物即外消旋顺式-12-氧代-PDA的非手性前体。
