Department of Biotechnology, Tokyo Institute of Technology, B-52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan.
Org Biomol Chem. 2019 Feb 27;17(9):2393-2402. doi: 10.1039/c8ob03196g.
(18R)- and (18S)-stereoisomers of resolvin E3 (RvE3), potent anti-inflammatory mediators, were synthesized stereo- and enantioselectively through the Wittig reaction of the carbonate of 6R,7R- and 6R,7S-dihydroxynona-2E,4E-dienal, a C12-C20 part, with the phosphonium salt corresponding to the C1-C11 part. The stereoisomeric carbonate was prepared by the Swern oxidation of 3-(AcO)-6R,7R- or 3-(AcO)-6R,7S-(dihydroxy-carbonate)-4-nonen-1-ol followed by the spontaneous elimination of the AcO group in one pot. The (6R,7R)-(dihydroxy-carbonate)-alcohol for (18R)-RvE3 was, in turn, provided by stereoselective epoxidation of 9-(TBS-oxy)nona-4Z,6E-dien-3R-ol with m-CPBA and the subsequent Pd-catalyzed addition of AcOH to the resulting syn vinyl epoxy alcohol followed by carbonate formation of the vic-syn-diol and TBS desilylation. The Mitsunobu inversion of the syn vinyl epoxy alcohol gave the anti isomer, which was converted to 3-(AcO)-6R,7S-(dihydroxy-carbonate)-4-nonen-1-ol, the intermediate to (18S)-RvE3, by the same set of reactions.
（18R）-和（18S）-分辨率 E3（RvE3）立体异构体，是有效的抗炎介质，通过 6R，7R-和 6R，7S-二羟基壬-2E，4E-二烯碳酸盐与相应的 C1-C11 部分的磷盐的Wittig 反应立体选择性和对映选择性合成。立体异构体碳酸盐通过 3-（AcO）-6R，7R-或 3-（AcO）-6R，7S-（二羟基碳酸酯）-4-壬-1-醇的 Swern 氧化制备，然后在一锅法中自发消除 AcO 基团。（6R，7R）-（二羟基碳酸酯）-醇，用于（18R）-RvE3，是通过 m-CPBA 对 9-（TBS-氧基）壬-4Z，6E-二烯-3R-醇进行立体选择性环氧化，然后 Pd 催化将 AcOH 加成到所得顺式乙烯环氧化醇，随后形成邻二醇的碳酸酯和 TBS 脱硅，得到的。顺式乙烯环氧化醇的 Mitsunobu 反转得到反式异构体，通过相同的反应序列将其转化为 3-（AcO）-6R，7S-（二羟基碳酸酯）-4-壬-1-醇，这是（18S）-RvE3 的中间体。
