Chemo-enzymatic approaches to morphine-6-glucuronide and selected analogues

• Main Author: Brady, Sarah Catherine
• Published: University of Edinburgh 1998
• Subjects: 547.7
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.641879

Morphine 1 is metabolised in the liver into its active form, morphine-6-glucuronide (M6G) 2. When M6G 2 is administered directly to patients it has greater analgesic potency than morphine 1 and this stimulated interest in the synthesis of M6G 2 as a novel analgesic. We have examined several synthetic routes to the precursor morphine-6-glucoside 4 with selective oxidation to M6G 2 as the final step. (Fig. 10917A). The coupling of a glucose residue to morphine 1 was investigated using both chemical and enzymatic approaches. However, selective oxidation at the C6' position of morphine-6-glucoside 4 did not yield the desired metabolite M6G 2. The replacement of the glucose reside in scheme 1 by galactose and arabinose gave morphine-6-glucoside analogues which are potentially an alternative source of analgesics. (Fig. 10917B).