δ1-四氢大麻酚的一种尿液代谢物。4",5"-双降-δ1-四氢大麻酚-7,3"-二酸的首次合成以及一种氘标记类似物。

A urinary metabolite of delta 1-tetrahydrocannabinol. The first synthesis of 4",5"-bisnor-delta 1-tetrahydrocannabinol-7,3"-dioic acid, and a deuterium labelled analogue.

作者信息

Szirmai M, Halldin M M

机构信息

Department of Pharmacognosy, Uppsala University, Sweden.

出版信息

Bioorg Med Chem. 1995 Jul;3(7):899-906. doi: 10.1016/0968-0896(95)00082-r.

DOI:10.1016/0968-0896(95)00082-r

PMID:7582966

Abstract

The first synthesis of unlabelled and [2H5]-labelled 4",5"-bisnor-delta 1-THC-7,3"-dioic acid, the major dicarboxylated urinary metabolite of delta 1-THC in man, is presented (preliminary results of this work have been presented in part at the Melbourne Symposium on Cannabis, Australia, September 1987, Ref. 1). The synthesis of methyl 3-(3,5-dihydroxyphenyl)-[3,3-2H2]-propanoate (8) is described in a nine step sequence from 3,5-dimethoxybenzoic acid in an overall yield of 24%. Compound 8 is condensed with a terpene synthon 9 under acidic conditions, acetylated and hydrolyzed with red HgO and HgCl2 to afford the 1-formyl-4",5",7-trisnor-delta 1-THC-3"-oic acid derivative (11). Compound 11 is oxidized using NaClO2 in 2-methyl-2-butene and hydrolyzed to give (+/-)-4",5"-bisnor-delta 1-THC-7,3"-dioic acid (12). The same approach has been used to prepare both the labelled and unlabelled metabolite.

摘要

首次合成了未标记的和[2H5]标记的4",5"-双降-δ1-四氢大麻酚-7,3"-二酸，它是人体中δ1-四氢大麻酚主要的二羧酸化尿液代谢物（这项工作的初步结果已部分发表于1987年9月在澳大利亚墨尔本举行的大麻研讨会上，参考文献1）。从3,5-二甲氧基苯甲酸出发，通过九步反应序列描述了3-(3,5-二羟基苯基)-[3,3-2H2]-丙酸甲酯（8）的合成，总产率为24%。化合物8在酸性条件下与萜类合成子9缩合，乙酰化，并用红色氧化汞和氯化汞水解，得到1-甲酰基-4",5",7-三降-δ1-四氢大麻酚-3"-酸衍生物（11）。化合物11在2-甲基-2-丁烯中用亚氯酸钠氧化并水解，得到(±)-4",5"-双降-δ1-四氢大麻酚-7,3"-二酸（12）。已采用相同方法制备了标记和未标记的代谢物。