Brown N K, Harvey D J
University Department of Pharmacology, Oxford, UK.
Eur J Drug Metab Pharmacokinet. 1988 Jul-Sep;13(3):165-76. doi: 10.1007/BF03189936.
n-Hexyl-delta-8-tetrahydrocannabinol (n-hexyl-delta-8-THC) and n-hexyl-delta-9-THC were synthesized by condensation of (1S)-cis-verbenol with 5-n-hexyl-1,3-dihydroxybenzene and administered intraperitoneally to male Charles-River CD-1 mice. Hepatic metabolites were isolated by solvent extraction and chromatography on Sephadex LH-20 and identified by GC/MS. Eleven metabolites were identified from n-hexyl-delta-8-THC and sixteen from n-hexyl-delta-9-THC. The pattern of metabolites was intermediate between that previously observed from the pentyl homologues and that from n-heptyl-delta-9-THC with the major biotransformation pathway being hydroxylation and oxidation at C-11. Other metabolites were mainly hydroxylated derivatives of these compounds. Metabolites containing two hydroxy groups in the side-chain were present in low concentration. These have not been observed from lower homologues but are major metabolites of n-heptyl-delta-9-THC. Compared with the metabolism of the n-pentyl homologue, there was a trend towards the production of more hydroxy metabolites at the expense of carboxylic acids, in keeping with the general reduction of oxidation observed with other homologous cannabinoids as the chain length increases.
正己基-δ-8-四氢大麻酚（n-己基-δ-8-THC）和正己基-δ-9-四氢大麻酚通过（1S）-顺式马鞭草烯醇与5-正己基-1,3-二羟基苯缩合合成，并腹腔注射给雄性Charles-River CD-1小鼠。通过溶剂萃取和Sephadex LH-20柱色谱法分离肝脏代谢产物，并通过气相色谱/质谱法进行鉴定。从正己基-δ-8-THC中鉴定出11种代谢产物，从正己基-δ-9-THC中鉴定出16种代谢产物。代谢产物模式介于先前观察到的戊基同系物和正庚基-δ-9-THC的模式之间，主要生物转化途径是C-11位的羟基化和氧化。其他代谢产物主要是这些化合物的羟基化衍生物。侧链含有两个羟基的代谢产物浓度较低。这些在较低同系物中未观察到，但却是正庚基-δ-9-THC的主要代谢产物。与正戊基同系物的代谢相比，存在以羧酸为代价产生更多羟基代谢产物的趋势，这与随着链长增加其他同源大麻素氧化普遍减少的情况一致。
