Morphine‐6β‐D‐glucuronide (M6βG), an active metabolite of morphine, and its isomer morphine‐6α‐D‐glucuronide (M6αG) were synthesized from 3‐O‐protected morphinethrough glycosylation and alkaline hydrolysis. All structures were determined by spectroscopic analysis, and especially it is the first time to report the single crystal of compound M6αG. In vitro binding assay showed that M6βG bound to mu opioid receptor (MOR), kappa opioid receptor (KOR), and delta opioid receptor (DOR) with nanomolar affinity (K_i = 28.03, 116.88, and 375.13 nM) and M6αG bound to them with similar affinity (K_i = 1070.13, 20 637.93, and 677.36 nM). The selectivity of M6αG toward KOR is much higher. Hot‐plate test showed that the analgesic effect of M6βG is better than that of M6αG, that is maybe because the mechanism of M6αG is different.

中文翻译：

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吗啡-6-葡萄糖醛酸苷异构体的合成与生物学评价

吗啡的活性代谢物吗啡-6β-D-葡糖醛酸（M6βG）及其异构体吗啡-6α-D-葡糖醛酸苷（M6αG）是通过3-O-保护的吗啡通过糖基化和碱性水解合成的。所有结构均通过光谱分析确定，尤其是首次报道了化合物M6αG的单晶。体外结合试验表明M6βG以纳摩尔亲和力（K _i = 28.03、116.88和375.13 nM）与mu阿片受体（MOR），κ阿片受体（KOR）和δ阿片受体（DOR）结合，而M6αG与它们结合以相似的亲和力（ķ_我= 1070.13、20 637.93和677.36 nM）。M6αG对KOR的选择性更高。热板试验表明，M6βG的镇痛作用优于M6αG，这可能是因为M6αG的作用机理不同。